Title of Invention	PYRAZOLE COMPOUNDS USEFUL AS PROTEIN KINASE INHIBITORS
Abstract	This invention describes novel pyrazole compounds of formula II: wherein Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1, 2, 4-triazinyl ring, and R2, R2, Rx, and Ry are as described in the specification. Ring C has an ortho substituent and is optionally substituted in the non-ortho positions. R2 and R2 are optionally taken together with their intervening atoms to form a fused ring system, such as an indazole ring; and Rx and Ry are optionally taken together with their intervening atoms to form a fused ring system, such as a quinazoline ring. The compounds are useful as protein kinase inhibitors, especially as

Title of Invention

PYRAZOLE COMPOUNDS USEFUL AS PROTEIN KINASE INHIBITORS

Abstract

This invention describes novel pyrazole compounds of formula II: wherein Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1, 2, 4-triazinyl ring, and R2, R2, Rx, and Ry are as described in the specification. Ring C has an ortho substituent and is optionally substituted in the non-ortho positions. R2 and R2 are optionally taken together with their intervening atoms to form a fused ring system, such as an indazole ring; and Rx and Ry are optionally taken together with their intervening atoms to form a fused ring system, such as a quinazoline ring. The compounds are useful as protein kinase inhibitors, especially as

Full Text	PYRAZOLE COMPOUNDS USEFUL AS PROTEIN KINASE INHIBITORS CROSS REFERENCE TO REIATED APPLICATIONS This application claims priority to US Provisional Patent Application 60/232,795 filed September 15, 2000, US Provisional Patent Application 60/257,887 filed December 21, 2000 and US Provisional Patent Application 60/286,949 filed April 27, 2001, the contents of which are incorporated herein by reference. FIELD OF THE INVENTION The present invention is in the field of medicinal chemistry and relates to compounds that are protein kinase inhibitors, compositions containing such compounds and methods of use. ore particularly, this invention relates to compounds that are inhibitors of GSK-3 and Aurora-2 protein kinases. The invention also relates to methods of treating diseases associated with these protein kinases, such as diabetes, cancer and Alzheimer's disease. BACKGROUND OF THE INVENTION The search for new therapeutic agents has been greatly aided in recent years by better understanding of the structure of enzymes and other biomolecules associated with target diseases. One important class of enzymes that has been the subject of extensive study is the protein kinases. Protein kinases mediate intracellular signal transduction. They do this by effecting a phosphoryl transfer from a nucleoside triphosphate to a protein acceptor that is involved in a signaling pathway. There are a number of kinases and pathways through which extracellular and other stimuli cause a variety of cellular responses to occur inside the cell. Examples of such stimuli include environmental and chemical stress signals (e.g. osmotic shock, heat shock, ultraviolet radiation, bacterial endotoxin, H2O2), cytokines (e.g. interleukin-1 (IL-l) and tumor necrosis factor a (TNF- ?)) , and growth factors (e.g. granulocyte macrophage- colony-stimulating factor (GM-CSF), and fibroblast growth factor (FGF). An extracellular stimulus may effect one or more cellular responses related to cell growth, migration, differentiation, secretion of hormones, activation of transcription factors, muscle contraction, glucose metabolism, control of protein synthesis and regulation of cell cycle. Many diseases are associated with abnormal cellular responses triggered by protein kinase-mediated events. These diseases include autoimmune diseases, inflammatory diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies and asthma, Alzheimer's disease or hormone-related diseases. Accordingly, there has been a substantial effort in medicinal chemistry to find protein kinase inhibitors that are effective as therapeutic agents. Aurora-2 is a serine/threonine protein kinase that has been implicated in human cancer, such as colon, breast and other solid tumors. This kinase is believed to be involved in protein phosphorylation events that regulate the cell cycle. Specifically, Aurora-2 may play a role in controlling the accurate segregation of chromosomes during mitosis. Misregulation of the cell cycle can lead to cellular proliferation and other abnormalities. In human colon cancer tissue, the aurora- 2 protein has been found to be overexpressed. See Bischoff et al., EMBO J., 1998, 17, 3052-3065; Schumacher et al., J. Cell Biol., 1998, 143, 1635-1646; Kimura et al., J. Biol. Chem., 1997, 272, 13766-13771. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase comprised of a and p isoforms that are each encoded by distinct genes [Coghlan et al., Chemistry & Biology, 7, 793-803 (2000); Kim and Kimmel, Curr. Opinion Genetics Dev., 10, 508-514 (2000)]. GSK-3 has been implicated in various diseases including diabetes, Alzheimer's disease, CNS disorders such as manic depressive disorder and neurodegenerative diseases, and cardiomyocete hypertrophy [WO 99/65897; WO 00/38675; and Haq et al., J. Cell Biol. (2000) 151, 117]. These diseases may be caused by, or result in, the abnormal operation of certain cell signaling pathways in which GSK-3 plays a role. GSK-3 has been found to phosphorylate and modulate the activity of a number of regulatory proteins. These proteins include glycogen synthase which is the rate limiting enzyme necessary for glycogen synthesis, the microtubule associated protein Tau, the gene transcription factor p-catenin, the translation initiation factor elF2B, as well as ATP citrate lyase, axin, .heat shock factor-1, c-Jun, c-Myc, c-Myb, CREB, and CEPBa. These diverse protein targets implicate GSK-3 in many aspects of cellular metabolism, proliferation, differentiation and development. In a GSK-3 mediated pathway that is relevant for the treatment of type II diabetes, insulin-induced signaling leads to cellular glucose uptake and glycogen synthesis. Along this pathway, GSK-3 is a negative regulator of the insulin-induced signal. Normally, the presence of insulin causes inhibition of GSK-3 mediated phosphorylation and deactivation of glycogen synthase. The inhibition of GSK-3 leads to increased glycogen synthesis and glucose uptake [Klein et al., PNAS, 93, 8455-9 (1996); Cross et al., Biochem. J., 303, 21-26 (1994); Cohen, Biochem. Soc. Trans., 21, 555-567 (1993); Massillon et al., Biochem J. 299, 123-128 (1994)]. However, in a diabetic patient where the insulin response is impaired, glycogen synthesis and glucose uptake fail to increase despite the presence of relatively high blood levels of insulin. This leads to abnormally high blood levels of glucose with acute and long term effects that may ultimately result in cardiovascular disease, renal failure and blindness. In such patients, the normal insulin-induced inhibition of GSK-3 fails to occur. It has also been reported that in patients with type II diabetes, GSK-3 is overexpressed [WO 00/38675]. Therapeutic inhibitors of GSK-3 are therefore potentially useful for treating diabetic patients suffering from an impaired response to insulin. GSK-3 activity has also been associated, with Alzheimer's disease. This disease is characterized by the well-known ?-amyloid peptide and the formation of intracellular neurofibrillary tangles. The neurofibrillary tangles contain hyperphosphorylated Tau protein where Tau is phosphorylated on abnormal sites. GSK-3 has been shown to phosphorylate these abnormal sites in cell and animal models. Furthermore, inhibition of GSK-3 has been shown to prevent hyperphosphorylation of Tau in cells [Lovestone et al., Current Biology 4, 1077-86 (1994); Brownlees et al., Neuroreport 8, 3251-55 (1997)]. Therefore, it is believed that GSK-3 activity may promote generation of the neurofibrillary tangles and the progression of Alzheimer's disease. Another substrate of GSK-3 is ?-catenin which is degradated after phosphorylation by GSK-3. Reduced levels of ?-catenin have been reported in schizophrenic patients and have also been associated with other diseases related to increase in neuronal cell death [Zhong et al., Nature, 395, 698-702 (1998); Takashima et al., PNAS, 90, 7789-93 (1993); Pei et al., J. Neuropathoi. Exp, 56, 70-78 (1997)]. As a result of the biological importance of GSK-3, there is current interest in therapeutically effective GSK-3 inhbitors. Small molecules that inhibit GSK-3 have recently been reported [WO 99/65897 (Chiron) and WO 00/38675 (SmithKline Beecham)]. For many of the aforementioned diseases associated with abnormal GSK-3 activity, other protein kinases have also been targeted for treating the same diseases. However, the various protein kinases often act through different biological pathways. For example, certain quinazoline derivatives have been reported recently as inhibitors of p38 kinase (WO 00/12497 to Scios). The compounds are reported to be useful for treating conditions characterized by enhanced p38-? activity and/or enhanced TGF-p activity. While p38 activity has been implicated in a wide variety of diseases, including diabetes, p38 kinase is not reported to be a constituent of an insulin signaling pathway that regulates glycogen synthesis or glucose uptake. Therefore, unlike GSK-3, p38 inhibition would not be expected to enhance glycogen synthesis and/or glucose uptake. There is a continued need to find new therapeutic agents to treat human diseases. The protein kinases aurora-2 and GSK-3 are especially attractive targets for the discovery of new therapeutics due to their important role in cancer, diabetes, Alzheimer's disease and other diseases. DESCRIPTION OF THE INVENTION It has now been found that compounds of this invention and pharmaceutical compositions thereof are effective as protein kinase inhibitors, particularly as inhibitors of aurora-2 and GSK-3. These compounds have the general formula I: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: Z1 to Z4 are as described below; Ring A is selected from the group consisting of: G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-member ed aryl or heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; R1 is selected from -halo, -CN, -N02, T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered.heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R8, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adj acent substituent taken together with their intervening atoms form said ring fused to Ring C; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3, and any substitutable nitrogen on said ring formed by Rx and Ry is substituted by R4; T is a valence bond or a C1-4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -N02, -CN, -S(O)R, -S(O)2R, "SR, -N(R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R-7)CO2 (optionally substituted Ci-6 aliphatic), -N(R4)N(R4)2f -C=NN(R4)2, -C=N-OR, -N (R7) CON(R7) 2, -N(R7)SO2N(R7)2, -N(R4)SO2R, or -OC (=O)N(R7) 2; each R is independently selected from hydrogen or an optionally substituted group selected from C3.-6 aliphatic, C6-io aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2(Ci-e aliphatic), -CON(R7)2, or -SO2R7; or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NO2/ -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) CO2(optionally substituted C1_6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R4) CON(R4) 2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC (=O)N(R4) 2, or R5 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; V is -O-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(R6)-, -N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N(R6)C(O)O-, -N(R6)CON(Re)-, -N(R6)SO2N(Re)-, -N(R6)N (R6) -, -C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C (R6)2N(R6) -, -C(R6)2N -C(Re)=N-O-, -C(R6)2N(R6)N(R6)-, -C (R6) 2N (R6) SO2N(Re) - , or -C (R6) 2N(R6) CON(R6) - ; W is -C(R6)2O-, -C{R6)2S-, -C{R6)2SO-, -C(Re)2SO2-, -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-, -C(R6)OC(0)-, -C(R6)OC(O)N(R6)-, -C(R6) 2N(R6) CO- , -C(R6)2N(R6)C(0)0-, -C(Rs)=NN(R6)-, -C(R6)=N-O-, -C(R6)2N(Re)N(R6)-, -C(R6)2N(R6)SO2N(R6)-, -C(R6)2N(R6)C0N(R6)-, or -CON(R6)-; each R6 is independently selected from hydrogen or an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1_6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; each R8 is independently selected from an optionally substituted C1-4 aliphatic group, -OR6, -SR6, -COR6, -SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or -CO2R6; and R9 is selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2/ -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=MN(R4)2f -C=N-OR, -N(R4)CON(R4)2, -N (R4) SO2N(R4) 2, -N(R4)S02R, or -OC(=O)N(R4)2.. As used herein, the following definitions shall apply unless otherwise indicated. The"phrase "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or with the term * (un> substituted." Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other. The term "aliphatic" as used herein means straight-chain, branched or cyclic C1-C12 hydrocarbons which are completely saturated or which contain one or more units of unsaturation but which are not aromatic. For example, suitable aliphatic groups include substituted or unsubstituted linear, branched or cyclic alkyl, alkenyl, alkynyl groups and hybrids thereof such as (eyeloalkyl)alkyl, (eyeloalkenyl)alkyl or (cycloalkyl)alkenyl. The terms "alkyl", "alkoxy", "hydroxyalkyl", "alkoxyalkyl" , and "alkoxycarbonyl", used alone or as part of a larger moiety includes both straight and branched chains containing one to twelve carbon atoms. The terms "alkenyl" and "alkynyl" used alone or as part of a larger moiety shall include both straight and branched chains containing two to twelve carbon atoms. The term "cycloalkyl" used alone or as part of a larger moiety shall include cyclic C3-C12 hydrocarbons which are completely saturated or which contain one or more units of unsaturation, but which are not aromatic. The terms "haloalkyl", "haloalkeriyl" and "haloalkoxy" means alkyl, alkenyl or alkoxy, as the case may be, substituted with one or more halogen atoms. The term "halogen" means F, Cl, Br, or I. The term "heteroatom" means nitrogen, oxygen, or sulfur and includes any oxidized form of nitrogen and sulfur, and the quaternized form of any basic nitrogen. Also the term ^nitrogen" includes a substitutable nitrogen of a heterocyclic ring. As an example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be K (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR+ (as in N-substituted pyrrol idinyl) . The terms "carbocycle", "carbocyclyl", "carbocyclo", or "carbocyclic" as used herein means an aliphatic ring system having three to fourteen members. The terms "carbocycle", "carbocyclyl", wcarbocyclo", or "carbocyclic" whether saturated or partially unsaturated, also refers to rings that are optionally substituted. The terms "carbocycle", "carbocyclyl", "carbocyclo", or "carbocyclic" also include aliphatic rings that are fused to one or more aromatic or nonaromatic rings, such as in a decahydronaphthyl or tetrahydronaphthyl, where the radical or point of attachment is on the aliphatic ring. The term "aryl" used alone or as part of a larger moiety as in "aralkyl", "aralkoxy", or "aryloxyalkyl", refers to aromatic'ring groups having five to fourteen members, such as phenyl, benzyl, phenethyl, 1-naphthyl, 2-naphthyl, 1-anthracyl and 2- anthracyl. The term "aryl" also refers to rings that are optionally substituted. The term "aryl" may be used interchangeably with the term "aryl ring". "Aryl" also includes fused polycyclic aromatic ring systems in which an aromatic ring is fused to one or more rings. Examples include 1-naphthyl, 2-naphthyl, 1-anthracyl and 2- anthracyl. Also included within the scope of the term "aryl", as it is used herein, is a group in which an aromatic ring is fused to one or more non-aromatic rings, such as in an indanyl, phenanthridinyl, or tetrahydronaphthyl, where the radical or point of attachment is on the aromatic ring. The term "heterocycle", "heterocyclyl", or "heterocyclic" as used herein includes non-aromatic ring systems having five to fpurteen members, preferably five to ten, in which one or more ring carbons, preferably one to four, are each replaced by a heteroatom such as N, O, or S. Examples of heterocyclic rings include 3-1H- benzimidazol-2-one, (1-substituted) -2-oxo-benzimidazol-3- yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2- tetrahydropyranyl, 3 - tetrahydropyranyl, 4- tetrahydropyranyl, [1,3]-dioxalanyl, [1,3]-dithiolanyl, [1,3 3 -dioxanyl, 2-tetrahydrothiophenyl, 3- tetrahydrothiophenyl, 2-morpholinyl, 3-morpholinyl, 4- morpholinyl, 2-thiomorpholinyl, 3-thlomorpholinyl, 4- thiomorpholinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3- pyrrolidinyl, 1-piperazinyl, 2-piperazinyl, 1- piperidinyl, 2 -piperidinyl, 3-piperidinyl, 4-piperidinyl, 4-thiazolidinyl, diazolonyl, N-substituted diazolonyl, l- phthalimidinyl, benzoxanyl, benzopyrrolidinyl, benzopiperidinyl, benzoxolanyl, benzothiolanyl, and benzothianyl. Also included within the scope of the term "heterocyclyl" " or "heterocyclic", as it is used herein, is a group in which a non-aromatic heteroatom-containing ring is fused to one. or more aromatic or non-aromatic rings, such as in an indolinyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl, where the radical or point of attachment is on the non-aromatic heteroatom-containing ring. The term "heterocycle", "heterocyclyl", or "heterocyclic" whether saturated or partially unsaturated, also refers to rings that are optionally substituted. The term "heteroaryl", used alone or as part of a larger moiety as in "beteroaralkyl" or "heteroarylalkoxy", refers to heteroaromatic ring groups having five to fourteen members. Examples of heteroaryl rings include 2-furanyl, 3-furanyl, N-imidazolyl, 2- imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4- isoxazolyl, 5-isoxazolyl, 2-oxadiazolyl, 5-oxadiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, l-pyrrolyl, 2- pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyfidyl, 2- pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 3-pyridazinyl, 2- thiazolyl, 4-thiazolyl, 5-thiazolyl, 5-tetrazolyl, 2- triazolyl, 5-triazolyl, 2-thienyl, 3-thienyl, carbazolyl, benzimidazolyl, benzothienyl, benzofuranyl, indolyl, quinolinyl, benzotriazolyl, benzothiazolyl, . benzooxazolyl, benzimidazolyl, isoquinolinyl, indolyl, isoindolyl, acridinyl, or benzoisoxazoyl. Also included within the scope of the term "heteroaryl", as it is used herein, is a group in which a heteroatomic ring is fused to one or more aromatic or nonaromatic rings where the radical or point of attachment is on the heteroaromatic ring. Examples include tetrahydroguinolinyl, tetrahydroisoquinolinyl, and pyrido[3,4-d]pyrimidinyl. The term "heteroaryl" also refers to rings that are optionally substituted. The term "heteroaryl" may be used interchangeably with the term "heteroaryl ring" or the term "heteroaromatic". An aryl (including aralkyl,. aralkoxy, aryloxyalkyl and the like) or heteroaryl (including heteroaralkyl and heteroarylalkoxy and the like) group may contain one or more substituents. Examples of suitable substituents on the unsaturated carbon atom of an aryl, heteroaryl, aralkyl, or heteroaralkyl group include a halogen, -R°, -0R°, -SR°/ 1,2-methylene-dioxy, 1,2-ethylenedioxy, protected OH (such as acyloxy), phenyl (Ph), substituted Ph, -O(Ph), substituted -O(Ph), -CH2(Ph), substituted -CH2 (Ph) , -CH2CH2(Ph), substituted -CH2CH2(Ph), -N02, -CN, -N(R°)2, -NR°C(O)R°, -NR°C (O)N(R°) 2, -NR°CO2R°, -NR°NR°C(O)R°, -NR°NR°C (O)N(R°) 2, -NR°NR°CO2R0, -C(O)C(O)R°, -C(O)CH2C(O)R°, -CO2R°, -C(O)R°, -C (0)N (R°) 2, -OC(O)N(R°)2, -S(O)2R°, -SO2N(R°)2/ -S (0) R°, -NR°SO2N (R°) 2/ -NR°S02R°, -C(=S)N(R°)2, -C (=NH)-N(R°) 2, - (CH2)yNHC (0)R°, - (CH2)yNHC(O)CH(V-Ro) (R°) ; wherein R° is hydrogen, a substituted or unsubstituted aliphatic group, an unsubstituted heteroaryl or heterocyclic ring, phenyl (Ph) , substituted Ph, -O(Ph), substituted -O(Ph), -CH2(Ph), or substituted -CH2(Ph); y is 0-6; and V is a linker group. Examples of substituents on the aliphatic group or the phenyl ring of R° include amino, alkylamino, dialkylamino, aminocarbonyl, halogen, alkyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkoxy, nitro, cyano, carboxy, alkoxycarbonyl, alkylcarbonyl, hydroxy, haloalkoxy, or haloalkyl. An aliphatic group or a non-aromatic heterocyclic ring may contain one or more substituents. Examples of suitable substituents on the saturated carbon of an aliphatic group or of a non-aromatic heterocyclic ring include those listed above for the unsaturated carbon of an aryl or heteroaryl group and the following: =0, =S, =NNHR, =NN(R)2, =N-, =NNHC(O)R, =NNHC02 (alkyl) , s=NNHSO2 (alkyl) , or =NR, where each R* is independently selected from hydrogen, an unsubstituted aliphatic group or a substituted aliphatic group. Examples of substituents on the aliphatic group include amino, alkylamino, dialkylamino, aminocarbonyl, halogen, alkyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkoxy, nitro, cyano, carboxy, alkoxycarbonyl, alkyl carbonyl, hydroxy, haloalkoxy, or haloalkyl. Suitable substituents on the nitrogen of a non- aromatic heterocyclic ring include -R+, -N(R+)2/ -C(O)R+, -CO2R+, -C(O)C(O)R+, -C(O)CH2C(O)R+, -SO2R+, -SO2N(R+)2, -C(=S)N(R+)2, -C(=NH) -N(R+)2/ and -NR+SO2R+; wherein R+ is hydrogen, an aliphatic group, a substituted aliphatic group, phenyl (Ph) , substituted Ph, -O(Ph), substituted -0 (Ph) , CH2(Ph), substituted CH2(Ph) , or an unsubstituted heteroaryl or heterocyclic ring. Examples of substituents on the aliphatic group or the phenyl ring include amino, alkylamino, dialkylamino, aminocarbonyl, halogen, alkyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkoxy, nitro, cyano, carboxy, alkoxycarbonyl, alkylcarbonyl, hydroxy, haloalkoxy, or haloalkyl. The term linker group" or "linker" means an organic moiety that connects two parts of a compound. Linkers are typically comprised of an atom such as oxygen, or sulfur, a unit such as -NH-, -CH2-, -C(0)-, -C(O)NH-, or a chain of atoms, such as an alkylidene chain. The molecular mass of a linker is typically in the range of about 14 to 200, preferably in the range of 14 to 96 with a length of up to about six atoms. Examples of linkers include a saturated or unsaturated Ci-6 alkylidene chain which is optionally substituted, and wherein one or two saturated carbons of the chain are optionally replaced by -0(0)-, -C(O)C(O)-, -CONH-, -CONHNH-, -C02-, -OC(O)-, -NHCOa-, -O-, -NHCONH-, -OC(O)NH-, -NHNH-, -NHCO-, -S-, -SO-, -S02-, -3SH-, -SO2NH-, or -NHSO2- . The term "alkylidene chain" refers to an optionally substituted, straight or branched carbon chain that may be fully saturated or have one or more units of unsaturation. The optional substituents are as described above for an aliphatic group. A combination of substituents or variables is permissible only if such a combination results in a stable or chemically feasible compound. A stable compound or chemically feasible compound is one in which the chemical structure is not substantially altered when kept at a temperature of 40 °C or less, in the absence of moisture or other chemically reactive conditions, for at least a week. Unless otherwise stated, structures depicted herein are also meant to include all stereochemical forms of the structure; i.e., the R and S configurations for each asymmetric center. Therefore, single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, structures depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by a 13C- or 14C-enriched carbon are within the scope -of this invention. Compounds of formula I or salts thereof may be formulated into compositions. In a preferred embodiment, the composition is a pharmaceutical composition. In one embodiment, the composition comprises an amount of the protein kinase inhibitor effective to inhibit a protein kinase, particularly GSK-3, in a biological sample or in a patient. In another embodiment, compounds of this invention and pharmaceutical compositions thereof, which comprise an amount of the protein kinase. inhibitor effective to treat or prevent a GSK-3-mediated condition and a pharmaceutically acceptable carrier, adjuvant, or vehicle, may be formulated for administration to a patient. The term "GSK-3-mediated condition" or "disease", as used herein, means any disease or other deleterious condition or state in which GSK-3 is known to play a role. Such diseases or conditions include., without limitation, diabetes, Alzheimer's disease, Huntington's Disease, Parkinson's Disease, AIDS- associated dementia, amyotrophic lateral sclerosis (AML), multiple sclerosis (MS), schizophrenia, cardiomycete hypertrophy, reperfusion/ischemia, and baldness. One aspect of this invention relates to a method of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, which method comprises administering to the patient a therapeutically effective amount of a compound of formula I or a pharmaceutical composition thereof. This method is especially useful for diabetic patients. Another method relates to inhibiting the production of hyperphosphorylated Tau protein, which is useful in halting or slowing the progression of Alzheimer's disease. Another method relates to inhibiting the phosphorylation of ?-catenin, which is useful for treating schizophrenia. Another aspect of the invention relates to inhibiting GSK-3 activity in a biological sample, which method comprises contacting the biological sample with a GSK-3 inhibitor of formula I. Another aspect of this invention relates to a method of inhibiting Aurora-2 activity in a patient, which method comprises administering to the patient a compound of formula I or a composition comprising said compound. Another aspect of this invention relates to a method of treating or preventing an Aurora-2-mediated disease with an Aurora-2 inhibitor, which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound of formula I or a pharmaceutical composition thereof. The term "Aurora-2-mediated condition" or "disease", as used herein, means any disease or other deleterious condition in which Aurora is known to play a role. The term "Aurora-2-mediated condition" or "disease" also means those diseases or conditions that are alleviated by treatment with an Aurora-2 inhibitor. Such conditions include, without limitation, cancer. The term "cancer" includes, but is not limited to the following cancers: colon and ovarian. Another aspect of the invention relates to inhibiting Aurora-2 activity in a biological sample, which method comprises contacting the biological sample with the Aurora-2 inhibitor of formula I, or a composition thereof. Another aspect of this invention relates to a method of treating or preventing a CDK-2-mediated diseases with a CDK-2 inhibitor, which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound of formula I or a pharmaceutical composition thereof. The term "CDK-2-mediated condition" or "disease", as used herein, means any disease or other deleterious condition in which CDK-2 is known to play a role. The term "CDK-2-mediated condition" or "disease" also means those diseases or conditions that are alleviated by treatment with a CDK-2 inhibitor. Such conditions include, without limitation, cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis, alopecia, and autoimmune diseases"such as rheumatoid arthritis. See Fischer, P.M. and Lane, D.P., Current Medicinal Chemistry, 7, 1213-1245 (2000); Mani, S., Wang, c., Wu, K., Francis, R. and Pe.stell, R., Exp. Opin. Invest. Drugs, 9, 1849 (2000); Fry, D.W. and Garrett, M.D. , Current Opinion in Oncologic, Endocrine & Metabolic Investiga.tiona.1 Drugs, 2, 40-59 (2000). Another aspect of the invention relates to inhibiting CDK-2 activity in a biological sample or a patient, which method comprises administering to the patient a compound of formula I or a composition comprising said compound. Another aspect of this invention relates to a method of treating or preventing an ERK-2-mediated diseases with an ERK-2 inhibitor, which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound of formula I or a pharmaceutical composition thereof. The term wERK-mediated condition", as used herein means any disease state or other deleterious condition in which ERK is known to play a role. The term ERK-2-mediated condition" or "disease" also means those diseases or conditions that are alleviated by treatment with a ERK-2 inhibitor. Such conditions include, without limitation, cancer, stroke, diabetes, hepatomegaly, cardiovascular disease including cardiomegaly, Alzheimer's disease, cystic fibrosis, viral disease, autoimmune diseases, atherosclerosis, restenosis, psoriasis, allergic disorders including asthma, inflammation, neurological disorders and hormone-related diseases. The term "cancer" includes, but is not limited to the following cancers: breast, ovary, cervix, prostate, testis, genitourinary tract, esophagus, larynx, glioblastoma, neuroblastoma, stomach, skin, keratoacanthoma, lung, epidermoid carcinoma, large cell carcinoma, small cell carcinoma, lung adenocarcinoma, bone, colon, adenoma, pancreas, adenocarcinoma, thyroid, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, sarcoma, bladder carcinoma, liver carcinoma and biliary passages, kidney carcinoma, myeloid disorders, lymphoid disorders, Hodgkin's, hairy cells, buccal cavity and pharynx (oral) , lip, tongue, mouth, pharynx, small intestine, colon- rectum, large intestine, rectum, brain and central nervous system, and leukemia. ERK-2 protein kinase and its implication in various diseases has been described [Bokemeyer et al. 1996, Kidney Int. 49, 1187; Anderson et al., 1990, Nature 343, 651; Crews et al., 1992, Science 258, 478; Bjorbaek et al., 1995, J. Biol. Chem. 270, 18848; Rouse et al., 1994, Cell 78, 1027; Raingeaud et al., 1996, Mol. Cell Biol. 16, 1247; Raingeaud et al. 1996; Chen et al., 1993 Proc. Natl. Acad. Sex. USA 90, 10952; Oliver et al., 1995, Proc. Soc. Exp. Biol. Med. 210, 162; Moodie et al., 1993, Science 260, 1658; Frey and Mulder, 1997, Cancer Res. 57, 628; Sivaraman et al., 1997, J Clin. Invest. 99, 1478; Whelchel et al., 1997, Am. J. Respir. Cell Mol. Biol. 16, 589]. Another aspect of the invention relates to inhibiting ERK-2 activity in a biological sample or a patient, which method comprises administering to the patient a compound of formula I or a composition comprising said compound. Another aspect of this invention relates to a method of treating or preventing an AKT-mediated diseases with an AKT inhibitor, which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound of formula I or a pharmaceutical composition thereof. The term "AKT-mediated condition", as used herein, means any disease state or other deleterious condition in which AKT is known to play a role. The term "AKT-mediated condition" or "disease" also means those diseases or conditions that are alleviated by treatment with a AKT inhibitor. AKT-mediated diseases or conditions include, but are not limited to, proliferative disorders, cancer, and neurodegenerative disorders. The association of AKT, also known as protein kinase B, with various diseases has been described [Khwaja) A., .Nature, pp. 33-34, 1990; Zang, Q. Y., et al, Oncogene, 19 2000; Kazuhiko, N., et al, The Journal of Neuroscience, 20 2000] . Another aspect of the invention relates to inhibiting AKT activity in a biological sample or. a patient, which method comprises administering to the patient a compound of formula I or a composition comprising said compound. Another aspect of this invention relates to a method of treating or preventing a Src-mediated disease with a Src inhibitor, which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound of formula I or a pharmaceutical composition thereof. The term wSrc-mediated condition", as used herein means any disease state or other deleterious condition in which Src is known to play a role. The term "Src-mediated condition" or "disease" also means those diseases or conditions that are alleviated by treatment with a Src inhibitor. Such conditions include, without limitation, hypercalcemia, osteoporosis, osteoarthritis, cancer, symptomatic treatment of bone metastasis, and Paget's disease. Src protein kinase and its implication in various diseases has been described [Soriano, Cell, 69, 551 (1992); Soriano et al., Cell, 64, 693 (1991); Takayanagi, J. Clin. Invest., 104, 137 (1999); Boschelli, Drugs of the Future 2000, 25(7), 717, (2000); Talamonti, J. Clin. Invest., 91, 53 (1993); Lutz, Biochem. Biophys. Res. 243, 503 (1998); Rosen, J. Biol. Chem., 261, 13754 (1986); Bolen, Proc. Natl. Acad. Sci. USA, 84, 2251 (1987); Masaki, Hepatology, 27, 1257 (1998); Biscardi, Adv. Cancer Res., 76, 61 (1999); Lynch, Leukemia, 7, 1416 (1993); Wiener, Clin. Cancer Res., 5, 2164 (1999); Staley, Cell Growth Diff., 8, 269 (1997)]. Another aspect of the invention relates to inhibiting Src activity in a biological sample or a patient, which method comprises administering to the patient a compound of formula I or a composition comprising said compound. The term "pharmaceutically acceptable carrier, adjuvant, or vehicle" refers to a non-toxic carrier, adjuvant, or vehicle that may be administered to a patient, together with a compound of this invention, and which does not destroy the pharmacological activity thereof. The term "patient" includes human and veterinary subjects. The term "biological sample", as used herein, includes, without limitation, cell cultures or extracts thereof; preparations of an enzyme suitable for in vitro assay; biopsied material obtained from a mammal or extracts thereof;" and blood, saliva, urine, feces, semen, tears, or other body fluids or extracts thereof. The amount effective to inhibit protein kinase for example, GSK-3 and Aurora-2, is one that measurably inhibits the kinase activity where compared to the activity of the enzyme in the absence of an inhibitor.- Any method may be used to determine inhibition, such as, for example, the Biological Testing Examples described below. Pharmaceutically acceptable carriers that may be used in these pharmaceutical compositions include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid," potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. The compositions of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. The term "parenteral" as used herein includes subcutaneous, intravenous, int r amus cular, intra - articular, intra - synovial, intrasternal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of this invention may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally- acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or di-glycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically- acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as carboxymethyl cellulose or similar dispersing agents which are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tweens, Spans and other emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation. The pharmaceutical compositions of this invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions or solutions. In ? the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents may also be added. Alternatively, the pharmaceutical compositions of this invention may be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non- irritating excipient which is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug. Such materials include cocoa butter, beeswax and polyethylene glycols. The pharmaceutical compositions of this invention may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs. Topical application for the lower intestinal tract can be effected in a rectal suppository formulation (see above) or in a suitable enema formulation. Topically-transdermal patches may also be used. For topical applications, the pharmaceutical compositions may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of the compounds of this invention include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, the pharmaceutical compositions can be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. For ophthalmic use, the pharmaceutical compositions may be formulated as micronized suspensions in isotonic, pH adjusted sterile saline, or, preferably, as solutions in isotonic, pH adjusted sterile saline, either with or without a preservative such as benzylalkonium chloride. Alternatively, for ophthalmic uses, the pharmaceutical compositions may be formulated in an ointment such as petrolatum. The pharmaceutical compositions of this invention may also be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other conventional solubilizing or dispersing agents. In addition to the compounds of this invention, pharmaceutically acceptable derivatives or prodrugs of the compounds of this invention may also be employed in compositions to treat or prevent the above-identified diseases or disorders. A "pharmaceutically acceptable derivative or prodrug" means any pharmaceutically acceptable salt, ester/ salt of an ester or other derivative of a compound of this invention which, upon administration to a recipient, is capable of providing, either directly or indirectly, a compound of this invention or an inhibitorily active metabolite or residue thereof. Particularly favored derivatives or prodrugs are those that increase the bioavailability of the compounds of this invention when such compounds are administered to a patient (e.g., by allowing an orally administered compound to be more readily absorbed into the blood) or which enhance delivery of the parent compound to a biological compartment (e.g., the brain or lymphatic system) relative to the parent species. Pharmaceutically acceptable prodrugs of the compounds of this invention include, without limitation, esters, amino acid esters, phosphate esters, metal salts and sulfonate esters. Pharmaceutically acceptable salts of the compounds of this invention include those derived from phaxmaceutically acceptable inorganic and organic acids and bases. Examples of suitable acid salts include acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, malonate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, tartrate, thiocyanate, tosylate and undecanoate. Other acids, such as oxalic, while not in themselves pharmaceutically acceptable, may be employed in the preparation of salts useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable acid addition salts. Salts derived from appropriate bases include alkali metal (e.g., sodium and potassium), alkaline earth metal (e.g., magnesium), ammonium and N+(C1_4 alkyl)4 salts. This invention also envisions the quaternization of any basic nitrogen-containing groups of the compounds disclosed herein. Water or oil-soluble or dispersible products may be obtained by such quaternization. The amount of the protein kinase inhibitor that may be combined with the carrier materials to produce a single dosage form will vary depending upon the patient treated and the particular mode of administration. Preferably, the compositions should be formulated so that a dosage of between 0.01 - 100 mg/kg body weight/day of the inhibitor can be administered to a patient receiving these compositions. It should also be understood that a specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, and the judgment of the treating physician and the severity of the particular disease being treated. The amount of the inhibitor will also depend upon the particular compound in the composition. Depending upon the particular protein kinase- mediated condition to be treated or prevented, additional therapeutic agents, which are normally administered to treat or prevent that condition, may be administered together with the inhibitors of this invention. For example, in the treatment of diabetes other anti-diabetic agents may be combined with the GSK-3 inhibitors of this invention to treat diabetes. These agents include, •without limitation, insulin or insulin analogues, in injectable or inhalation form, glitazones, alpha glucosidase inhibitors, biguanides, insulin sensitizers, and sulfonyl ureas. Other examples of agents the inhibitors of this invention may also be combined with include, without limitation, chemotherapeutic agents or other anti- proliferative agents such as adriamycin, dexamethasone, vincristine, cyclophosphamide, fluorouracil, topotecan, taxol, interferons, and platinum derivatives; anti- inflammatory agents such as corticosteroids, TNF blockers, IL-1 KA, azathioprine, cyclophosphamide, and sulfasalazine; immunomodulatory and immunosuppressive agents such as cyclosporin, tacrolimus, rapamycin, mycophenolate mofetil, interferons, corticosteroids, cyclophophamide, azathioprine, and sulfasalazine; neurotrophic factors such as acetylcholinesterase inhibitors, MAO inhibitors, interferons, anti- convulsants, ion channel blockers, riluzole, and anti-. Parkinsonian agents; agents for treating cardiovascular disease such as beta-blockers, ACE inhibitors, diuretics, nitrates, calcium channel blockers, and statins; agents for treating liver disease such as corticosteroids, cholestyramine, interferons, and anti-viral agents; agents for treating blood disorders such as corticosteroids, anti-leukemic agents, and growth factors; and agents for treating immunodeficiency disorders such as gamma globulin. Those additional agents may be administered separately from the protein kinase inhibitor-containing composition, as part of a multiple dosage regimen. Alternatively, those agents may be part of a single dosage form, mixed together with the protein kinase inhibitor of this invention in a single composition. Compounds of this invention may exist in alternative tautomeric forms, as in tautomers 1 and 2 shown below. Unless otherwise indicated, the representation of either tautomer is meant to include the other. Rx and Ry (at positions Z3 and Z4, respectively) may be taken together to form a fused ring, providing a bicyclic ring system containing Ring A. Preferred Rx/Ry rings include a 5-, 6-, 7-, or 8-membered unsaturated or partially unsaturated ring having 0-2 heteroatoms, wherein said Rx/Ry ring is optionally substituted. Examples of Ring A systems are shown below by compounds I-A through I-DD, wherein Z1 is nitrogen or C(R9) and Z2 is nitrogen or C(H). Preferred bicyclic Ring A systems include I-A, I-B, I-C, I-D, I-E, I-F, I-G, I-H, I-I, I-J, I-K, I-L, and I-M, more preferably I-A, I-B, i-c, I-F, and I-H, and most preferably I-A, I-B, and I-H. In the monocyclic Ring A system, preferred Rx groups, when present, include hydrogen, alkyl- or dialkylamino, acetamido, or a C1_4 aliphatic group such as methyl, ethyl, cyclopropyl, isopropyl or t-butyl. Preferred Ry groups, when present, include T-R3 wherein T is a valence bond or a methylene, and R3 is -R, -N(R4)2, or -OR. Examples of preferred Ry include 2-pyridyl, 4- pyridyl, piperidinyl, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or dialkylamino, acetamido, optionally substituted phenyl such as phenyl or halo- substituted phenyl, and methoxymethyl. In the bicyclic Ring A system, the ring formed when RX and Ry are taken together may be substituted or unsubstituted. Suitable substituents include -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02/ -CN, -S(O)R, -S02R, -SR, -N(R4)2/ -CON(R4)2, -SO2N(R4)2, -O.C(=O)R, -N(R4)COR, -N(R4) C02(optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2, -N(R4)SO2N(R4)2/ -N(R4)SO2R, or -OC (=O)N(R4) 2, wherein R and R4 are as defined above. Preferred Rx/Ry ring substituents include -halo, -R, -OR, -COR, -CO2R, -CON(R4)2/ -CN, or -N(R4)2 wherein R is hydrogen or an optionally substituted C1-g aliphatic group. R2 and R2' may be taken together to form a fused ring, thus providing a bicyclic ring system containing a pyrazole ring. Preferred fused rings include benzo, pyrido, pyrimido, and a partially unsaturated 6-membered carbocyclo ring, wherein said fused ring is optionally substituted. These are exemplified in the following formula I compounds having a pyrazole-containing bicyclic ring system: Preferred substituents on the R2/R2' fused ring include one or more of the following: -halo, -N(R4)2/ -C1_3 alkyl, -Ca-3 haloalkyl, -NO2, -0(C1-3 alkyl) , -CO2(C1-3 alkyl) , -CN, -SO2 (C1-3 alkyl) , -SO2NH2, -OC(O)NH2/ - NH2SO2(C1_3 alkyl) , -NHC(O) (C1-3 alkyl) , -C(O)NH2, and-CO(Ci- 3 alkyl) , wherein the (C1-3 alkyl) is most preferably methyl. When the pyrazole ring system is monocyclic, preferred R2 groups include hydrogen, C1-4 aliphatic, alkoxycarbonyl, (un) substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N- heterocyclyl) carbonyl. Examples of such preferred R2 substituents include methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH20CH2Ph, CH2CH2CH2NH2/ CH2CH2CH2NHCOOC (CH3)3/ CONHCH(CH3.)2/ CONHCH2CH=CH2, CONHCH2CH2OCai3, CONHCH2Ph, CONH (cyclohexyl) , CON (Et) 2, CON (CH3) CH2Ph, CONH (n- C3H7) , CON(Et)CH2CH2CH3, CONHCH2CH (CH3) 2, CON (n-C3H7) 2, CO(3- methoxymethylpyrrolidin-1-yl) , CONH(3-tolyl) , CONH(4- tolyl) , CONHCH3, CO(morpholin-l-yl) , C0(4-methylpiperazin- 1-yl) , CONHCH2CH2OH, CONH2, and CO (piperidin-1-yl) . A preferred R2' group is hydrogen. An embodiment that is particularly useful for treating GSK3 -mediated diseases relates to compounds of formula II: or a pharmaceutically acceptable derivative or prodrug thereof, wherein; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any subs ti tut able non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R8, said C1-6 aliphatic group optionally, substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with the.ir intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3, and any substitutable nitrogen on said ring formed by Rx and Ry is substituted by R4; T is a valence bond or a C1_4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -N02, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -NO2, -CN, -S(O)R, -S(0)2R, -SR, -N(R4)2, -CON(R7)2, -SO2N(R7)2,-OC(=O)R, -N(R7)COR, -N(R7)C02 (optionally substituted QL-G aliphatic), -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R7) CON (R7) 2, -N(R7)SO2N(R7)2, -N(R4)SO2R7 or -OC (=O)N(R7) 2; each R is independently selected from hydrogen or an optionally substituted group selected from Ci-6 aliphatic, C6.10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected, from -R7, -COR7, -CO2 (optionally substituted d-e aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02/ -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -C0N(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted Ci-6 aliphatic), -N(R4)N(R4)2, -C=NN(R4)2/ -C=N-OR, -N(R4) CON(R4)2, -N(R4)SO2N(R4)2, -N{R4)SO2R, or -OC (=O)N(R4) 2/ or R5 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; V is -O-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(Re)-, -N(R6)-, -CO-, -CQ2-, -N(R6)CO-, -N(R6)C(O)O-, -N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(R6)N(R6) -, -C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN(R6) - , -C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C(R6) 2N(R6) SO2N(R6) - , or -C (R6) 2N (R6) CON (R6) - ; W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-, -C(R6)OC(O)-, -C(R6)OC(O)N(R6)-, -C(R6) 2N(R6) CO-, -C(R6)2N(R6)C(O)O-, -C(Re)=NN(R6)-, -C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C(R6)2N(R6)SO2N(R6)-, -C(R€)2N(R€)CON(R6)-, or -CON(R6)-; each R€ is independently selected from hydrogen, an optionally substituted Ca_4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen.to form a 5-8 membered heterocyclyl or heteroaryl ring; and each R8 is independently selected from an optionally substituted C1_4 aliphatic group, -OR6, -SR6, -COR6, -SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or -CO2R6. When the Rx and RY groups of formula II are taken together to form a fused ring, preferred R/Ry rings include a 5-, 6-, 7-, or 8-membered unsaturated or partially unsaturated ring having 0-2 heteroatoms, wherein said R/Ry ring is optionally substituted. This provides a bicyclic- ring system containing a pyrimidine ring. Examples of preferred pyrimidine ring systems of formula II are the mono- and bicyclic systems shown below. More preferred pyrimidine ring systems of formula II include II-A, II-B, II-C, II-F, and II-H, most preferably II-A, II-B, andll-H. In the monocyclic pyrimidine ring system of formula II, preferred R groups include hydrogen, alkyl- or dialkylamino, acetamido, or a Ci_4 aliphatic group such as methyl, ethyl, cyclopropyl, isopropyl or t-butyl. Preferred Ry groups include T-R3 wherein T is a valence bond or a methylene, and R3 is -R, -N(R4)2/ or -OR. When R3 is -R or -OR, a preferred R is an optionally substituted group selected from C1-6 aliphatic, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring. Examples of preferred Ry include. 2-pyridyl, 4-pyridyl, piperidinyl, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or dialkylamino, acetamido, optionally substituted phenyl such as phenyl or halo-substituted phenyl, and methoxymethyl. In the bicyclic pyrimidine ring system of formula II, the ring formed when Rx and Ry are taken together may be substituted or unsubstituted. Suitable substituents include -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02/ -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N (R4) C02 (optionally substituted C1-c aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N(R4) SO2N(R4) 2/ -N(R4) SO2R, or -OC(=O)N(R4)2, wherein R and R4 are as defined above. Preferred Rx/Ry ring substituents include -halo, -R, -OR, -COR, -CO2R, -CON(R4)2, -CN, or -N(R4)2 wherein R is an optionally substituted d-g aliphatic group. The R2 and R2' groups of formula II may be taken together to form a fused ring, thus providing a bicyclic ring system containing a pyrazole ring. Preferred fused rings include benzo, pyrido, pyrimido, and a partially unsaturated 6-membered carbocyclo ring. These are exemplified in the following formula II compounds having a pyrazole-containing bicyclic ring system: Preferred substituents on the R2/R2' fused ring of formula II include one or more of the following: -halo, -N(R4)2, -d-4 alkyl, -cx_4 haloalkyl, -N02l -0(Cx_4 alkyl), -C02 (d-4 alkyl) , -CN, -SO2 (d_4 alkyl), -SO2NH2/ -OC(O)NH2, -NH2SO2 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(O)NH2/ and -CO(Ca-4 alkyl) , wherein the (Ci_4 alkyl) is a straight, branched, or cyclic alkyl group. Preferably, the (C1-4 alkyl) group is methyl. When the pyrazole ring system of formula II is monocyclic, preferred R2 groups include hydrogen, a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1_6 aliphatic group. Examples of such preferred R2 groups include methyl, t-butyl, -CH2OCH3, cyclopropyl, furanyl, thienyl, and phenyl. A preferred R2' group is hydrogen. More preferred ring systems of formula II are the following, which may be substituted as described above, wherein R2 and R2' are taken together with the pyrazole ring to form an indazole ring; and Rx and Ry are each methyl, or Rx and Ry are taken together with the pyrimidine ring to form a quinazoline or tetrahydroquinazoline ring: Particularly preferred are those compounds of formula II-Aa, II-Ba, or II-Ha wherein ring C is a phenyl ring and R1 is halo, methyl, or trifluoromethyl. Preferred formula II Ring C groups are phenyl and pyridinyl. When two adjacent substituents on Ring C are taken together to form a fused ring, Ring C is contained in a bicyclic ring system. Preferred fused rings include a benzo or pyrido ring. Such rings preferably are fused at ortho and meta positions of Ring C. Examples of preferred bicyclic Ring C systems include naphthyl, guinolinyl and isoguinolinyl. An important feature of the formula II compounds is the R1 ortho substituent on Ring C. An ortho position on Ring C or Ring b is defined relative to the • position where Ring A is attached. Preferred R1 groups include -halo, an optionally substituted C1-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(RS)2, -CO2R6, -CONH2, -NHCOR6, -OC(0)NH2, or -NHSO2R6. When R1 is an optionally substituted Ci-6 aliphatic group, the most preferred optional substituents are halogen. Examples of preferred R1 groups include -CF3, -Cl, -F, -CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2CH3, -CH3, -CF2CH3, cyclohexyl, t- butyl, isopropyl, cyclopropyl, -C=CH, -C=C-CH3, -SO2CH3, -SO2NH2, -N(CH3)2, -CO2CH3, -CONH2, -NHCOCH3, -OC(O)NH2, -NHSO2CH3, and -OCF3. On Ring C of formula II, preferred R5 substituents, when present, include -halo, -CN, -N02, -N(R4)2, optionally substituted C1_6 aliphatic group, -OR, -C(O)R, -C02R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4)SO2R. More preferred R5 .substituents include -Cl, -F, -CN, -CF3, -NH2, -NH(d-4 aliphatic), -N(C1_4 aliphatic)2, -O(C1_4 aliphatic), C1 aliphatic, and -CO2(C1-4 aliphatic). Examples of such preferred Rs substituents include -Cl, -F, -CN, -CF3, -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl, cyclopropyl, isopropyl, .t- butyl, and -CO2Et. Preferred formula II compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring; (b) Rx is hydrogen or C1-4 aliphatic and Ry is T-R3, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted 5-7 membered unsaturated or partially unsaturated ring having 0-2 ring nitrogens; (c) R1 is -halo, an optionally substituted Ca_6 aliphatic group, phenyl, -COR6, -ORS, -CN, -SO2R6, -SO2NH2, -N(R6)2/ -CO2R6, -CONH2, -NHCOR6, -QC(O)NH2, or -NHSO2RG; and (d) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a Cx-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring. More preferred compounds of formula II have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring; (b) Rx is hydrogen or methyl and Ry is -R, N(R4)2, or -OR, or Rx and Ry are taken together with their intervening atoms to form a 5-7 membered unsaturated or partially unsaturated carbocyclo ring optionally substituted with -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, . -NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2/ -OC(=O)R, -N(R4)C0R, -N(R4) CO2 (optionally substituted d_6 aliphatic), -N(R4)N(R4)2/ -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N(R4) SO2N(R4) 2, -N(R4)SO2R, or -OC(=O)N(R4)2; (c) R1 is -halo, a Ci_6 haloaliphatic group, a Ci_6 aliphatic group, phenyl, or -CN; (d) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, or a C1_6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and (e) each R5 is independently selected from -halo, -CN, -N02/ -N(R4)2, optionally substituted C1_6 aliphatic group, -OR, -C(O)R, -CO2R, -C0NH(R4) , -N(R4)COR, -SO2N(R4)2, or -N(R4)SO2R. Even more preferred compounds of formula II have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl ring optionally substituted by -R5; (b) RX is hydrogen or methyl and Ry is methyl, methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or an optionally substituted group selected from 2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted benzo ring or partially unsaturated 6-membered carbocyclo ring; (c) R1 is -halo, a C1 aliphatic group optionally substituted with halogen, or -CN; (d) R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring (a) optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -C1-4 haloalkyl, -N02, -0(C1-4 alkyl) , -CO2(c1 alkyl) , -CN, - SO2 (C1-4 alkyl) , - SO2NH2, -OC (O) NH2, -NH2SO2 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl), -C(0)NH2, or -CO(CX.4 alkyl) , wherein the (C1_4 alkyl) is a straight, branched, or cyclic alkyl group; and (e) each R5 is independently selected from -Cl, -F, -C3ST, -CF3, -NH2, -NH(C1-4 aliphatic) , -N(C1-4 aliphatic)2, -O(C1-4 aliphatic), C1-4 aliphatic, and -CO2(C1_4 aliphatic). Representative compounds of formula II are shown below in Table 1. In another embodiment, this invention provides a composition comprising a compound of formula II and a pharmaceutically acceptable carrier. One aspect of this invention relates to a method of inhibiting GSK-3 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula II. Another aspect relates to a method of treating a disease that is alleviated by treatment with a GSK-3 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula II. Another aspect relates to a method of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula II. This method is especially useful for diabetic patients. Another aspect relates to a method of . inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula II. This method is especially useful in halting or slowing the progression of Alzheimer's disease. Another aspect relates to a method of inhibiting the phosphorylation of p-catenin in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula II. This method is especially useful for treating schizophrenia. One aspect of this invention relates to a method of inhibiting Aurora activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula II. Another aspect relates to a method of treating a disease that is alleviated by treatment with an Aurora inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula II. This method is especially useful for treating cancer, such as colon, ovarian, and breast cancer. One aspect of this invention relates to a method of inhibiting CDK-2 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula II. ... Another aspect relates to a method of treating a disease that is alleviated by treatment with a CDK-2 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula II. This method is especially useful for treating cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis, alopecia, and autoimmune diseases such as rheumatoid arthritis. Another method relates to inhibiting GSK-3, Aurora, or CDK-2 activity in a biological sample, which method comprises contacting the biological sample with the GSK-3 or Aurora inhibitor of formula II, or a pharmaceutical composition thereof, in an amount effective to inhibit GSK-3, Aurora or CDK-2. Each of the aforementioned methods directed to the inhibition of GSK-3, Aurora or CDK-2, or the treatment of a disease alleviated thereby, is preferably carried out with a preferred compound of formula II, as described above. Another embodiment of this invention relates to compounds of formula III: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; Rx and Ry are taken together with their intervening atoms to form a fused, benzo ring or a 5-8 membered carbocyclo ring, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3; T is a valence bond or a C1_4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2/ is substituted by R4; R3 is selected from -R, -halo, =0, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -N02, -CN, -S(O)R, -S(0)2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted C1-6 aliphatic), -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON (R4) 2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -0C (=0)N(R4) 2; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -C02 (optionally substituted C1-g aliphatic) , -C0N(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form, a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2/ -CON{R4)2/ -SO2N(R4)2/ -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted d-e aliphatic), -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R4) CON (R4) 2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -0C (=0)N (R4) 2 ; V.is -0-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(Re)-, -N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N(R6) C (O) O-, -N(R6)CON(R6)-, -N(RG)SO2N(R6)-, -N(R6)N(R6) -, -C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(R6)2S-, -C(Re)2SO-, -C(R6)2SO2-# -C(R6)2SO2N(R6)-, -C(R6)2N(R6) -, -C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C(R6) =NN(R6) -, -C(R6)=N-O-, -C{R6)2N(R6)N(R6)-, -C (R6) 2N(R6) SO2N(R6) -, or -C(R6)2N(R6)CON(R6)-; W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -C02-, -C(R6)OC(O)-, -C(R6)OC(O)N(R6)-, -C (R6) 2N(R6) CO-, -C(R6)2N -C (R6) 2N (R6) N (R6) - , -C (R6) 2N (R6) SO2N (R6) -, -C(R6)2N{R6)CON(R6)-, or -CON(R6)-; each R6 is independently selected from hydrogen or an optionally substituted C1_4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; and each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring. Preferred formula III Ring D monocyclic rings include substituted and unsubstituted phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings. When two adjacent substituents on Ring D are taken together to form a fused ring, the Ring D system is bicyclic. Preferred formula III Ring D bicyclic rings include 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3 -dihydro- 1H-isoindolyl, 2,3 -dihydro- 1H-indolyl, isoguinolinyl, quinolinyl, and naphthyl. Examples of more preferred bicyclic Ring D systems include naphthyl and isoquinolinyl. Preferred R5 substituents on Ring D of formula III include halo, oxo, CN, -N02, -N(R4)2, -CO2R, -CONH(R4) , -N(R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1_6 aliphatic. More preferred R5 substituents include -halo, -CN, -oxo, -SR, -OR, -N(R4)2/ -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. Examples of Ring D substituents include -OH, phenyl, methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, C=CH, Cl, Br, F, I, NH2, C(O)CH3, i-propyl, tex-t-butyl, SEt, OMe, N(Me)2, methylene dioxy, and ethylene dioxy. Preferred rings formed when the Rx and Ry groups of formula III are taken together to form a fused ring include a 5-, 6-, or 7-membered unsaturated or partially unsaturated carbocyclo ring, wherein any substitutable carbon on said fused ring is substituted by oxo or T-R3. Examples of preferred bicyclic ring systems are shown below. Preferred substituents on the Rx/Ry fused ring of formula III include -R, oxo, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02/ -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)C0R,' -N(R4) CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2/ -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N (R4) SO2N(R4) 2, -N(R4)SO2R, or -OC(=O)N(R4)2\|. wherein R and R4 are as defined above. More preferred substituents on the Rx/Ry fused ring include halo, CN, oxo, Ca-g alkyl, C1 alkoxy, (C1_6 alkyl) carbonyl, (C1.6 alkyl) sulfonyl, mono- or dialkylamino, mono- or dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy, or 5-6 membered heteroaryl. Examples of such preferred substituents include methoxy, methyl, isopropyl, methylsulfonyl, cyano, chloro, pyrrolyl, methoxy, ethoxy, ethylamino, acetyl, and acetamido. Preferred R2 substituents of formula III include hydrogen, C1 -4aliphatic, alkoxycarbonyl, (un) substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylatninocarbonyl, and (N- heterocyclyl)carbonyl. Examples of such preferred R2 substituents include methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3/ CH20H, CH2OCH3/ CH2CH2CH2OH, C352C3l2CH2OCH3, CH2CH2CH2OCH2Phf CH2CH2CH2NH2, CH2CH2CH2NHCOOC(CH3) 3/ CONHCH(CH3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl) , CON(Et)2, CON(CH3) CH2Ph, CONH (n-C3H7) , CON(Et)CH2CH2CH3, CONHCH2CH (CH3)2, CON(n-C3H7) 2/ CO(3- methoxymetliylpyrrolidin-1 -yl) , CONH (3 -tolyl), CONH (4 - tolyl) , CONHCH3/ CO(morpholin-l-yl) , CO (4-methylpiperazin- 1-yl) , CONHCH2CH2OH, CONH2, and CO(piperidin-l-yl) . When the R2 and R2' groups of formula III are taken together to form a ring, preferred R2/R2' ring, systems containing the pyrazole ring include benzo, pyrido, pyrimido, 3-oxo-2H-pyridazino, and a partially unsaturated 6-membered carbocyclo ring. Examples of such preferred R2/R2' ring systems containing the pyrazole ring include the following: Preferred substituents on the R2/R2' fused ring of formula III include one or more of the following: -halo, -N(R4)2, -C1 alkyl, -Ca_4 haloalkyl, -N02/ -0(d-4 alkyl) , -CO2(C1-4 alkyl) , -CN, - SO2 (C1_4 alkyl) , -SO2NH2, -OC(O)NH2/ -NH2SO2(C1_4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(O)NH2/ and -CO(C1-4 alkyl) , wherein the (d-4 alkyl) is a straight, branched, or cyclic alkyl group. Preferably, the (C1_4 alkyl) group is methyl. Preferred formula III compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring b is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4-tetrahydroisoguinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro-lff-isoindolyl, 2,3- dihydro-lff-indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; (b) Rx and Ry are taken together with their intervening atoms to form an optionally substituted benzo ring or a 5-7 membered carbocyclo ring; and (c) R2' is hydrogen or methyl and R2 is T-W-R6 or R, wherein W is -C(R6)2O-, -C(R6) 2N(R6) -, -CO-, -C02-, -C(R6)OC(O)-, -C(R6)2N(R6)CO-, -C (R6)2N (R6) C (O) 0-, or -CON(R6)-, and R is an optionally substituted group selected from C1-6 aliphatic or phenyl, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstitutedbenzo, pyrido, pyrimido, or partially unsaturated 6-membered carbocyclo ring. More preferred compounds of formula III have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or naphthyl; (b) RX and Ry are taken together with their intervening atoms to form a benzo ring or a 5-7 membered carbocyclo ring optionally substituted with -R, oxo-, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2/ -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted Cx.6 aliphatic) , (a) -N(R4)N(R4)2, -C=NN(R4)2/ -C=N-OR, -N(R4) CON(R4)2/ -N (c) each R5 is independently selected from halo, oxo, CN, NO2/ -N(R4)2, -CO2R, -CONH(R4) , -N(R4)COR, -SO2N(R4)2/ -N(R4)SO2R, -SR, -OR, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. Even more preferred compounds of formula III have one or more, and more preferably all, of the features selected from the group consisting of: (a) Rx and Ry are taken together with their intervening atoms to form a benzo or 6-membered partially unsaturated carbocyclo ring optionally substituted with halo, CN, oxo, C1_6 alkyl, Cx-e alkoxy, (C1-6 alkyl) carbonyl, (C1-6 alkyl) sulfonyl, mono- or dialkylamino, mono- or dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy, or 5-6 membered heteroaryl; (b) each R5 is independently selected from -halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-i0 aryl, or Ca_6 aliphatic; and (c) R2' is hydrogen and R2 is selected from R2' is hydrogen or methyl and R2 is T-W-R6 or R, wherein W is -C(R6)2O-, -C(R6)2N(R6)-, -CO-, -CO2-, -C (R6) OC (0)-, -C(R6)2N(R€)CO-, or -CON(R6)-, and R is an optionally substituted group selected from C1_6 aliphatic or phenyl, or R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -d-4 haloalkyl, -N02, -O(C1-4 alkyl), -CO2(d-4 alkyl) , -CN, -S02 (C1-4 alkyl), -SO2NH2,' -OC(O)NH2, -NH2SO2(C1-4 alkyl) , -NHC(0) (C1-4 alkyl), -C(0)NH2, or -CO(C1-4 alkyl), wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group. Representative compounds of formula III are set forth in Table 2 below. In another embodiment, this invention provides a composition comprising a compound of formula III and a pharmaceutically acceptable carrier. One aspect of this invention relates to a method of inhibiting GSK-3 activity in a patient, comprising administering to the patient -a therapeutically effective amount of a composition comprising a compound of formula III. Another aspect relates to a method of treating a disea.se that is alleviated by treatment with a GSK-3 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula III. Another aspect relates to a method of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula III. This method is especially useful for diabetic patients. Another aspect relates to a method of inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula III. This method is especially useful in halting or slowing the progression of Alzheimer's disease. Another aspect relates to a method of inhibiting the phosphorylation of ?-catenin in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula III. This method is especially useful for treating schizophrenia. One aspect of this invention relates to a method of inhibiting Aurora activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula III. Another aspect relates to a method of treating a disease that is alleviated by treatment with an Aurora inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula III. This method is especially useful for treating cancer, such as colon, ovarian, and breast cancer. One aspect of this invention relates to a method of inhibiting CDK-2 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula III. Another aspect relates to a method of treating a disease that is alleviated by treatment with a CDK-2 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of- a composition comprising a compound of formula III. • This method is especially useful for treating cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis, alopecia, and autoimmune diseases such as rheumatoid arthritis. One aspect of this invention relates to a method of inhibiting Src activity in a patient, comprising administering to the patient a therapeutically effective amount, of a composition comprising a compound of formula III. Another aspect relates to a method of treating a disease that is alleviated by treatment with a Src inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula III. This method is especially useful for treating hypercalcemia, osteoporosis, osteoarthritis, cancer, symptomatic treatment of bone metastasis, and Paget's disease. Another method relates to inhibiting GSK-3, Aurora, CDK-2, or Src activity in a biological sample, which method comprises contacting the biological sample with, the GSK-3, Aurora, CDK-2, or Src inhibitor of formula III, or a pharmaceutical composition thereof, in an amount effective to inhibit GSK-3, Aurora, CDK-2, or Src. Each of the aforementioned methods directed to the inhibition of GSK-3, Aurora, CDK-2, or Src, or the treatment of a disease alleviated thereby, is preferably carried out with a preferred compound of formula III, as described above. Compounds of formula III, wherein R2' is hydrogen and RX and Ry are taken together with the pyrimidine ring to form an optionally substituted guinazoline ring system, are also inhibitors of ERK-2 and AKT protein kinases. Accordingly, another method of this invention relates to a method of inhibiting ERK-2 or AKT activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula III, wherein R2 is hydrogen and Rx and Ry are taken together with the pyrimidine ring to form an optionally substituted quinazoline ring system. Another aspect relates to a method of treating a disease that is alleviated by treatment with a ERK-2 or AKT inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula III, wherein R2' is hydrogen and Rx and Ry are taken together with the pyrimidine ring to form an optionally substituted quinazoline ring system. This method is especially useful for treating cancer,, stroke, hepatomegaly, cardiovascular disease, Alzheimer's disease, cystic fibrosis, viral disease, autoimmune diseases, restenosis, psoriasis, allergic disorders including asthma, inflammation, and neurological disorders. Another embodiment of this invention relates to compounds of formula IV: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 1-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any.substitutable carbon on said fused ring is optionally and independently substituted by T-R3, and any substitutable nitrogen on said ring is substituted by R4; T is a valence bond or a C1_4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring containing 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein said fused ring is optionally substituted by up to three groups independently selected from halo, oxo, -CN, -NO2, -R7, or -V-R6; R3 is selected from -R, -halo, =0, -OR, -C(=O)R, -C02R, -COCOR, -COCH2COR, -NO2/ -CN, -S(O)R, -S(O)2R, -SR, -N(R4)2, -C0N(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)C0R, -N(R4)C02 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -ON-QR, -N(R4) C0N(R4) 2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2; each R is independently selected from hydrogen or an optionally substituted group selected from C1_6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1_6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2/ -SO2N(R4)2, -OC(=O)R, -N(R4)C0R, -N(R4)CO2 (optionally substituted C1_6 aliphatic), -N(R4)N(R4)2/ -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4)2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2; V is -O-, -S-, -SO-, -S02-, -N(R6)SO2-, -SO2N(R6)-, -N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N (R6) C (O) O-, -N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(RG) N(R6) -, -C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(Re)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C (R6) 2N(R6) - , -C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN(R6) - , -C(R6)=N-O-, -C(R6)2N(R6)N(RG)-, -C (R6) 2N(R6) SO2N(R6)-, or -C (R€) 2N (R6) CON (R€) - ; W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-, -C(R6)OC(O)-, -C(R6)OC(O)N(R€)-, -C (R6) 2N(R6) CO-, -C(R6)2N(R6)C(O)O-, -C(R6)=NN(R6)-, -C (R6) =N-O-, -C (R6) 2N (R6) N (R6) -, -C (R6) 2N (R6) S02N (R6) - , -C(R6)2N(R6)CON(RS)-, or -CON(R6)-; each R6 is independently selected from hydrogen or an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; and each R7 is independently selected from hydrogen or an optionally substituted C1-G aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl ring or heteroaryl. Preferred formula IV Ring D monocyclic rings include substituted and unsubstituted phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings. Preferred formula IV Ring D bicyclic rings include 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, 2,3-dihydro-lH-isoindolyl, 2, 3-dihydro-lH-indolyl, isoquinolinyl, quinolinyl, and naphthyl. Examples of more preferred Ring D bicyclic rings include naphthyl and isoquinolinyl. Preferred substituents on Ring D of formula IV include halo, oxo, CN, -NO2, -N(R4)2, -C02R, -CONH(R4) , -N(R4)COR, -SO2:N(R)2, -N{R4)SO2R, -SR, -OR, -C(O)R, or substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-io &ryl, or Cx-6 aliphatic. More preferred Rs substituents include -halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. Examples of Ring D substituents include -OH, phenyl, methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, GsCH, Cl, Br, F, I, NH2, C(O)CH3, i-propyl, tert-butyl, SEt, OMe, N(Me)2, methylene dioxy, and ethylene dioxy. When the Rx and Ry groups of formula IV are taken together to form a fused ring, preferred RX/RY rings include a 5-, 6-, 7-, or 8-membered unsaturated or partially unsaturated ring having 1-2 heteroatoms. This • provides a bicyclic ring system containing the pyrimidine ring. Examples of preferred pyrimidine ring systems of formula IV are the mono- and bicyclic systems shown below. More preferred pyrimidine ring systems of formula IV include IV-E, IV-G, IV-H, IV-J, IV-K, rv-L, IV-M, rv-T, and IV-U. In the monocyclic pyrimidine ring system of formula IV, preferred Rx groups include hydrogen, amino, nitro, alkyl- or dialkylamino, acetamido, or a C1-4 aliphatic group such as methyl, ethyl, cyclopropyl, isopropyl or t-butyl. preferred Ry groups include T-R3 wherein T is a valence bond or a methylene, and R3 is -R, -N(R4)2, or -OR. When R3 is -R or -OR, a preferred R is an optionally substituted group selected from C1-6 aliphatic, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring. . Examples of preferred Ry groups include 2-pyridyl, 4-pyridyl, piperidinyl, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or dialkylamino, acetamido, optionally substituted phenyl such as phenyl, methoxyphenyl, trimethoxyphenyl, or halo-substituted phenyl, and methoxymethyl. In the bicyclic pyrimidine ring system of formula IV, the. ring formed when RX and Ry are taken together may be substituted or unsubstituted. Suitable substituents include -R, halo, -OR, -C(=o)R, -co2R, -COCOR, -N02f -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -C0N(R4)2, -SO2N(R4}2, -OC(=O)R, -N(R4)COR, -N(R4) C02 (optionally substituted C1-6 aliphatic), -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N(R4} SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2, wherein R and R4 are as defined above for compounds of formula IV. Preferred Rx/Ry ring substituents include -halo, -R, -OR, -COR, -CO2R, -CON(R4)2/ -CN, or -N(R4)2 wherein R is a substituted or unsubstituted C1_s aliphatic group. The R2 and R2' groups of formula IV may be taken together to form a fused ring, thus providing a bicyclic ring system containing a pyrazole ring. Preferred fused rings include benzo, pyrido, pyrimido, and a partially unsaturated 6-membered carbocyclo ring. These are exemplified in the following formula IV compounds having a pyrazole-containing bicyclic ring system: Preferred substituents on the R /R fused ring of formula IV include one or more of the following: -halo, -N(R4)2, -C1-4 alkyl, -C1-4 haloalkyl, -N02/ -O(CC1_4 alkyl) , -CO2(C1-4 alkyl) , -CN, -S02 (C1-4 alkyl), -SO2NH2, -OC(O)NH2, -NH2SO2(C1-4 alkyl) , -NHC(O) (C3.-4 alkyl) , -C(O)NH2, and - CO (C1-4 alkyl) , wherein the (C1_4 alkyl) is a straight, branched, or cyclic alkyl group. Preferably, the (C1-4 alkyl) group is methyl. When the pyrazole ring system of formula IV is monocyclic, preferred R2 groups include hydrogen, a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1 -6 aliphatic group. Examples of such preferred R2 groups include methyl, t-butyl, -CH2OCH3, cyclopropyl, furanyl, thienyl, and phenyl. A preferred R2' group is hydrogen. Preferred formula IV compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro-IS-isoindolyl, 2,3- dihydro-lff-indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; (b) Rx is hydrogen or C3.-4 aliphatic and Ry is T- R3, or Rx and Ry are taken together with their intervening atoms to form an. optionally substituted 5-7. metobered unsaturated or partially unsaturated ring having 1-2 ring heteroatoms; and (c) R2' is hydrogen or methyl and R2 is T-W-Rs or R, wherein W is -C(Rs)jO-, -C(Rfi) 2N(R6) -, -CO-, -C02-, -C(R6)OC(O)-, -C(R6)2N{R6)CO-, -C (R6)2N(R6) C (O) O-, or -CON(R6)-, and R is an optionally substituted group selected from C1-6 aliphatic or phenyl, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido, or partially unsaturated 6-membered carbocyclo ring. More preferred compounds of formula IV have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4- tetrahydroisoguinolinyl, 1,2,3,4-tetrahydroquinolinyl, 2,3- dihydro - Iff- i soindolyl, 2,3- dihydro - Iff- indolyl, isoquinolinyl, quinolinyl, or naphthyl; (b) Rx is hydrogen or methyl and Ry is -R, N(R4)2/ or -OR, or Rx and Ry are taken together with their intervening atoms to form a 5-7 membered unsaturated or partially unsaturated ring having- 1-2 ring nitrogens, wherein said ring is optionally substituted with -R, halo, oxo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -C0N(R4)2 -SO2N(R4}2, -OC(=O)R, -N(R4)C0R, -N(R4)CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2, -N(R4)SO2N(R4)2/ -N(R4)SO2R, or -OC (=O)N(R4) 2; and (c) each R5 is independently selected from halo, oxo, CN, N02, -N(R4)2, -CO2R, -C0NH(R4), -N{R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. Even more preferred compounds of formula IV have one or more, and more preferably all, of the features selected from the group consisting of: (a) Rx and Ry are taken together with their intervening atoms to form a 6-membered unsaturated or partially unsaturated ring having 1-2 ring nitrogens, optionally substituted with halo, CN, oxo, C1_6 alkyl, C1-6 alkoxy, (C1-6 alkyl) carbonyl, (C1-6 alkyl) sulfonyl, mono- or dialkylamino, mono- or dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy, or 5-6 membered heteroaryl; (b) each R5 is independently selected from -halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic; and (c) R2' is hydrogen and R2 is T-W-R6 or R, wherein W is -C(R6)2O-, -C(R6)2N(R6)-, -CO-, -C02-, -C(R6)OC(O)-, -C(R6)2N(R6)CO-, or -CON(R6)-, and R is an optionally substituted group selected from C1-6 aliphatic or phenyl, or R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, oxo, -N(R4)2, -C1-4 alkyl, -C1-4 haloalkyl, -N02, -O(C1 alkyl) , -C02 (C1-4 alkyl), -CN, -SO2(C1-4 alkyl) , -SO2NH2, -0C(0)NH2, -NH2SO2 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(o)NH2, or -CO(C1-4 alkyl) , wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group. (a) In another embodiment, this invention provides a composition comprising a compound of; formula IV and a pharmaceutically acceptable carrier. One aspect of this invention relates to a method of inhibiting GSK-3 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula IV. Another aspect relates to a method of treating a disease that is alleviated by treatment with a GSK-3 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula IV. Another aspect relates to a method of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, comprising administering to said patient a therapeutic ally effective amount of a composition comprising a compound of formula XV. This method is especially useful for diabetic patients. Another aspect relates to a method of inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula IV. This method is especially useful in halting or slowing the progression of Alzheimer's disease. Another aspect relates to a method of inhibiting the phosphorylation of p-catenin in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula IV. This method is especially useful for treating schizophrenia. One aspect of this invention relates to a method of inhibiting Aurora activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula IV. Another aspect relates to a method of treating a disease that is alleviated by treatment with an Aurora inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula IV. This method is especially useful for treating cancer, such as colon, ovarian, and breast cancer. One aspect of this invention relates to a method of inhibiting CDK-2 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula IV. Another aspect relates to a method of treating a disease that is alleviated by treatment with a CDK-2 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula IV. This method is especially useful for treating cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis, alopecia, and autoimmune diseases such as rheumatoid arthritis. Another method relates to inhibiting GSK-3, Aurora, or CDK-2 activity in a biological sample, which method comprises contacting the biological sample with the GSK-3 or Aurora inhibitor of formula IV, or a pharmaceutical composition thereof, in an amount effective to inhibit GSK-3, Aurora or CDK-2. Each of the aforementioned methods directed to the inhibition of GSK-3, Aurora or CDK-2, or the treatment of a disease alleviated thereby, is preferably carried out with a preferred compound of formula IV, as described above. Another embodiment of this invention relates to compounds of formula V: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: Z1 is N, CRa, or OR and Z2 is H or CH, provided that one of Z1 and Z2 is nitrogen; G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -RB; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -R5 is hydrogen at each, ortho carbon position of Ring D; R1 is selected from -halo, -CN, -N02; T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1_6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R8, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3, and any substitutable nitrogen on said ring formed by RX and Ry is substituted by R4; T is a valence bond or a C1_4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -NO2/ -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -NO2, -CN, -S(O)R, -S(O)2R, -SR, -N(R4)2, -CON(R7)2, -S02N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7)CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R7) CON(R7)2, -N(R7)SO2N(R7)2, -N(R4)SO2R, or -OC (=O)N(R7) 2; each R is independently selected from hydrogen or an optionally substituted gxoup selected from C1_6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2/ -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted C1-6 aliphatic) -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R4) CON (R4) 2/ -N(R4)SO2N(R4)2 -N(R4)SO2R, or -OC (=O)N(R4) 2 or R5 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; V is -O-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(R6)-, -N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N (R6) C (O) O-, -N(R6)CON(R6)-, -N(RG)SO2N(R6)-, -N(R6) N(R6) - , -C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-/ -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6) 2N (R6) - , -C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN (R6) - , -C(R6)=N-O-, -C(R6)2N(RG)N(R6)-, -C (R6) 2N(R6) SO2N(R6) - , or -C(R6)2N(R6)CON(R6)-; W is -C(R6)2O-, -C(R€)2S-, -C(R6)2SO-, -C(R6)2SO2-7 -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-, -C(Re)OC(O)-, -C(R6)OC(O)N(R6)-, -C (R6) 2N(Re) CO-, -C(R6)2N(R6)C(O)O-, -C(R6)=NN(R6)-, -C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C(R6)2N(R6)SO2N(R6)-, -C(R6)2N(R6)CON(R6)-, or -CON(R6)-; each R6 is independently selected from hydrogen, an optionally substituted C1_4 aliphatic group, or two RG groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1_6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; each R8 is independently selected from an optionally substituted C1-4 aliphatic group, -OR6, -SR6, -COR6, -SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -NO2, -CON(R6)2, or -CO2R6; and Ra is selected from halo, -OR, -C(=O)R, -C02R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N(R4) SO2N(R4) 2, -N(R4)SO2R, -OC(=O)N(R4)2, or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms. Compounds of formula V may be represented by specifying Z1 and Z2 as shown below: When the Rx and Ry groups of formula V are taken together to form a fused ring, preferred Rx/Ry rings include a 5-, S-, 1-, or 8-tnembered unsaturated or partially unsaturated ring having 0-2 heteroatoms, wherein said Rx/Ry ring is optionally substituted. This provides a bicyclic ring system containing a pyridine ring. Examples of preferred bicyclic ring systems of formula V are shown below. More preferred bicyclic ring systems of formula V include Va-A, Vb-A, Vc-A, Va-B, Vb-B, Vc-B, Va-D, Vb-D, Vc-D, Va-E, Vb-E, Vc-E, Va-J, Vb-J, Vc-J, Va-K, Vb-K, Vc-K, Va-L, Vb-L, Vc-L, Va-M, Vb-M, and Vc-M, most preferably Va-A, Vb-A, Ve-A, Va-B, Vb-B, and Vc-B. In the monocyclic pyridine ring system of formula V, preferred RX groups include hydrogen, alkyl- or dialkylamino, acetamido, or a C1_4 aliphatic group such as methyl, ethyl, cyclopropyl, isopropyl or t-butyl. Preferred Ry groups include T-R3 wherein T is a valence bond or a methylene, and R3 is -R, -N(R4)2/ or -OR. When R3 is -R or -OR, a preferred R is an optionally substituted group selected from C1-e aliphatic, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring. Examples of preferred Ry include 2-pyridyl, 4-pyridyl, piperidinyl, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, alley 1- or dialkylamino, acetamido, optionally substituted phenyl such as phenyl or halo-substituted phenyl, and methoxymethyl. In the bicyclic ring system of formula V, the ring formed when RX and Ry are taken together may be substituted or unsubstituted. Suitable substituents include -R, halo, -OR, -C(=O)R, -CO2R, -C0COR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=o)R, -N(R4)C0R, -N(R4)CO2 (optionally substituted C1-6 aliphatic), -N(R4)N(R4)2/ -C=NN(R4)2/ -ON-OR, -N(R4)CON(R4)2, -N(R4)SO2N(R4)2/ -N(R4)SO2R, or -OC(=O)N(R4)2, wherein R and R4 are as defined above. Preferred Rx/Ry ring substituents include -halo, -R, -OR, -COR, -CO2R, -CON(R4)2, -CN, or -N(R4)2 wherein R is an optionally substituted C1-6 aliphatic group. The R2 and R2' groups of formula V may be taken together to form a fused ring, thus providing a bicyclic ring system containing a pyrazole ring. Preferred fused rings include benzo, pyrido, pyrimido, and a partially unsaturated 6-membered carbocyclo ring. These are exemplified in the following formula V compounds having a pyrazole-containing bicyclic ring system: Preferred substituents on the R2/R2' fused ring of formula V include one or more of the following: -halo, -N(R4)2, -C1-4 alkyl, -QL-4 haloalkyl, -N02/ -0(C1_4 alkyl) , -CO2(C1-4 alkyl) , -C3N, -SO2(d_4 alkyl) , -SO2NH2, -OC(O)NH2, -NH2SO2(C1-4 alkyl) , -NHC(O) (d.4 alkyl) , -C(O)NH2/ and -CO (C2-4 alkyl), wherein the (C1 alkyl) is a straight, branched, or cyclic alkyl group. Preferably, the (Ca-4 alkyl) group is methyl. When the pyrazole ring system is monocyclic, preferred R2 groups include hydrogen, C1_4 aliphatic, alkoxycarbonyl, (un) substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N- heterocyclyl)carbonyl. Examples of such preferred R2 substituents include methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3/ CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC (CH3)3, CONHCH(CH3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH (cyclohexyl) , CON (Et) 2, CON (CH3) CH2Ph, CONH (n-C3H7) , CON(Et)CH2CH2CH3, CONHCH2CH (CH3) 2, CON (n-C3H7) 2, C0(3- methoxymethylpyrrolidin-1-yl), CONH (3 - tolyl) , CONH (4 - tolyl) , CONHCH3, CO (morpholin-1-yl) , C0(4-methylpiperazin- 1-yl) , CONHCH2CH2OH, CONH2, and CO (piperidin-1-yl) . A preferred R2' group is hydrogen. More preferred ring systems of formula V are the following, which may be substituted as described above, wherein R2 and R2' are taken together with the pyrazole ring to form an optionally substituted indazole ring; and Rx and Ry are each methyl, or Rx and Ry are taken together with the pyridine ring to form an optionally substituted quinoline, isoguinoline, tetrahydroquinoline or tetrahydroisoquinoline ring: When G is Ring C, preferred formula V Ring C groups are phenyl and pyridinyl. When two adjacent substituents on Ring C are taken together to form a fused ring, Ring C is contained in a bicyclic ring system. Preferred fused rings include a benzo or pyrido ring. Such rings preferably are fused at ortho and meta positions of Ring C. Examples of preferred bicyclic Ring C systems include napbthyl and isoquinolinyl. Preferred R1 groups include -halo, an optionally substituted Ci-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6. When R1 is an optionally substituted c1-6 aliphatic group, the most preferred optional substituents are halogen. Examples of preferred R1 groups include -CF3, -Cl, -F, -CN, -COCH3, -OCH3, -OH, -CH2CH3/ -OCH2CH3, -CH3, -CF2CH3, cyclohexyl, t-butyl, isopropyl, cyclopropyl, -CsCH, -CsC-CH3, -SO2CH3, -SO2NH2, -N(CH3)2, -CO2CH3, -CONH2, -NHCOCH3, -0C(0)NH2, -NHSO2CH3/ and -OCF3. On Ring C preferred R5 substituents, when present, include -halo, -CN, -N02, -N(R4)2, optionally substituted Cx.6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4)SO2R. More preferred R5 substituents include -Cl, -F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2 -0(C1_4 aliphatic), C1_4 aliphatic, and -CO2(Ci_4 aliphatic). Examples of such preferred R5 substituents include -Cl, -F, -CN, -CF3, -NH2/ -NHMe7 -NMe2/ -OEt, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, and -CO2Et. When G is Ring D, preferred formula V Ring D monocyclic rings include substituted and unsubstituted phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings. When two adjacent substituents on Ring D are taken together to form a fused ring, the Ring D system is bicyclic. Preferred formula V Ring D bicyclic rings include 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, quinolinyl, and naphthyl. Examples of more preferred bicyclic Ring D systems include naphthyl and isoguinolinyl. Preferred substituents on Ring D of formula V include one or more of the following: halo, oxo, CN, -N02, -N(R4)2, -Co2R, -CONH(R4), -N(R4)C0R, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6_10 aryl, or C1_6 aliphatic. More preferred Ring D substituents include -halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. Examples of Ring D substituents include -OH, phenyl, methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, OsCH, Cl, Br, F, I, NH2, C(O)CH3, i-propyl, tert-butyl, SEt, OMe, N(Me)2; methylene dioxy, and ethylene dioxy. Preferred formula V compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring, and R1 is -halo, an optionally substituted C1_6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHS02R6; or Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4- tetrahydroisoguinolinyl, 1,2,3,4-tetrahydroguinolinyl, 2, 3 -dihydro-lH-isoindolyl, 2, 3-dihydro-lH-indolyl, isoguinolinyl, quinolinyl, or naphthyl ring,- (b) Rx is hydrogen or C1-4 aliphatic and Ry is T- R3, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted 5-7 membered unsaturated or partially unsaturated ring having 0-2 ring nitrogens; and (c) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, . heteroaryl, or a C1_6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring. More preferred compounds of formula V have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic group, phenyl, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3- dihydro - 1H- isoindolyl, 2,3- dihydro-lH-indolyl, isoguinolinyl, quinolinyl, or naphthyl; (b) Rx is hydrogen or methyl and Ry is -R, N(R4)2, or -OR, or Rx and Ry are taken together with their intervening atoms to form a benzo ring or a 5-7 membered partially unsaturated carbocyclo ring, said benzo or carbocyclo ring optionally substituted with -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2/ -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2/ -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4) 2; (c) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, or a C1-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and (d) Ring D is substituted by oxo or R5, wherein each R5 is independently selected from -halo, -CN, -N02, -N(R4)2, optionally substituted C1_6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, or -N(R4)SO2R. Even more preferred compounds of formula V have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1_4 aliphatic group optionally substituted with halogen, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroguinolinyl, isoguinolinyl, quinolinyl, or naphthyl; (b) Rx is hydrogen or methyl and Ry is methyl, methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or an optionally substituted group selected from 2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry are taken together with their intervening atoms to form a benzo ring or a 6-membered partially unsaturated carbocyclo ring optionally substituted with halo, CN, oxo, C1-6 alkyl, C1_6 alkoxy, (C1-6 alkyl) carbonyl, (C1_6 alkyl)sulfonyl, mono- or dialkylamino, mono- or dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy, or 5-6 metnbered heteroaryl; (c) R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2 -C1-4 alkyl, -C1-4 haloalkyl, -N02, -0(03.-4 alkyl) , -CO2(C1-4 alkyl) , -CN, -SO2(C1_4 alkyl) , -SO2NH2, -OC(O)NH2, -NH2SO2 (Ca-4 alkyl) , -NHC(O) (C1.4 alkyl) , -C(O)NH2, or -CO (C1-4 alkyl) , wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl" group; and (d) Ring D is substituted by oxo or R5, wherein each R5 is independently selected from -Cl, -F, -CN, -CF3, -NH2, -NH(C1_4 aliphatic), -N(C1_4 aliphatic)2/ -O(C1-4 aliphatic), C1_4 aliphatic, and -C02(C1_4 aliphatic). Representative compounds of formula V are set forth in Table 4 below. In another embodiment, this invention provides a composition comprising a compound of formula V and a pharmaceutically acceptable carrier. One aspect of this invention relates to a method of inhibiting GSK-3 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula V. Another aspect relates to a method of treating a disease that is alleviated by treatment with a GSK-3 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula V. Another aspect relates to a method of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprisinq- a compound of formula V. This method is especially useful for diabetic patients. Another aspect relates to a method of inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula V. This method is especially useful in halting or slowing the progression of Alzheimer's disease. Another aspect relates to a method of inhibiting the phosphorylation of P-catenin in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula V. This method is especially useful for treating schizophrenia. One aspect of this invention relates to a method of inhibiting Aurora activity in a patient, comprising administering to the.patient a therapeutically effective amount of a composition comprising a compound of formula V. Another aspect relates to a method of treating a disease that is alleviated by treatment with an Aurora inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula V. This method is especially useful for treating cancer, such as colon, ovarian, and breast cancer. One aspect of this invention relates to a method of inhibiting CDK-2 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula V. Another aspect relates to a method of treating a disease that is alleviated by treatment with a CDK.-2 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula V. This method is especially useful for treating cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis, alopecia, and autoimmune diseases such as rheumatoid arthritis. Another method relates to inhibiting GSK-3, Aurora, or CDK-2 activity in a biological sample, which method comprises contacting the biological sample with the GSK-3 or Aurora inhibitor of formula V, or a pharmaceutical composition thereof, in an amount effective to inhibit GSK-3, Aurora or CDK-2. Each of the aforementioned methods directed to the inhibition of GSK-3, Aurora or CDK-2, or the treatment of a disease alleviated thereby, is preferably carried out with a preferred compound of formula V, as described above. Another embodiment of this invention relates to compounds of formula VI: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8 ; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R8, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Ry is T-R3'; T is a valence bond or a C1-4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4; R3 is an optionally substituted group selected from C1-6 aliphatic, C3-10 carbocyclyl, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1_6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each Rs is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)C0R, -N(R4)CO2 (optionally substituted C1_6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2/ -C=N-OR, -N(R4) CON (R4) 2/ -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4) 2, or Rs and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; V is -0-, -S-, -SO-, -SO2-, -N(R6-N(R6) C (0) O- , -N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(R6)N(R6) -, -C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C (R6) 2N(R6) - , -C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN(R6) - , -C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C(R6) 2N(R6) SO2N(R6) - , or -C(R6)2N(R6)CON(R6) -; W is -C(R6)2O-, -C(R6)2S-, -C(R6)2S0-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -C02-, -C(R6)OC(O)-, -C(R6)OC(O)N(R6)-, -C (R6) 2N(R6) CO- , -C(R6)2N(R6)C(O)O-, -C(R6)=NN(R6)-, -C (R6) =N-O-, -C(R6) 2N(R6)N(R6) - , -C (R6) 2N(R6) SO2N(R6) - , -C(R6)2N(R6)CON(R6)-, or -CON(R6)-; each R6 is independently selected from hydrogen, an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1_6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; and each R8 is independently selected from an optionally substituted C1_4 aliphatic group, -OR6, -SR6, -COR6, -SO2R6, -N(RG)2, -N(RG)N{R6)2, -CN, -N02, -CON(R6)2, or -CO2R6. Preferred Ry groups of formula VI include T-R3 wherein T is a valence bond or a methylene, and R3' is an optionally substituted group selected from C3.-6 aliphatic, C3-10 carbocyclyl, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms. A preferred R3' group is an optionally substituted group selected from C3_6 carbocyclyl, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring. Examples of preferred Ry include 2-pyridyl, 4-pyridyl, piperidinyl, morpholinyl, cyclopropyl, cyclohexyl, and optionally substituted phenyl such as phenyl or halo-substituted phenyl. The R2 and R2' groups of formula VT may be taken together to form a fused ring, thus providing a bicyclic ring system containing a pyrazole ring. Preferred fused rings include benzo, pyrido, pyrimido, and a partially unsaturated 6-membered carbocyclo ring. These are exemplified in the following formula VI compounds having a pyrazole-containing bicyclic ring system: Preferred substituents on the R2/R2' fused ring include one or more of the following: -halo, -N(R4)2, -Ci_4 alkyl, -d-4 haloalkyl, -NO2, -O(d-4 alkyl) , -CO2(C1-4 alkyl) , -CN, -SO2(C1-4 alkyl) , -SO2NH2/ -OC(O)NH2, -NH2SO2(Ca-4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(0)NH2, and -C0(C1-4 alkyl), wherein the (C1 alkyl) is a straight, branched, or cyclic alkyl group. Preferably, the (C1-4 alkyl) group is methyl. When the pyrazole ring system is monocyclic> preferred R2 groups of formula VI include hydrogen, C1-4 aliphatic, alkoxycarbonyl, (un)substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N- heterocyclyDcarbonyl. Examples of such preferred R2 substituents include methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, oyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC (CH3) 3 CONHCH(CH3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl) , CON(Et)2, CON(CH3)CH2Ph, CONH(n-C3H7) , CON(Et)CH2CH2CH3, CONHCH2CH (CH3) 2,( CON(n-C3H7) 2, C0(3- methoxymethylpyrrolidin-l-yl), CONH(3-tolyl), C0NH(4- tolyl) , CONHCH3, CO(morpholin-l-yl) , C0(4-methylpiperazin- 1-yl), COMHCH2CH2OH, CONH2, and CO(piperidin-l-yl). A preferred R2' group is hydrogen. When G is Ring C, preferred formula VI Ring C groups are phenyl and pyridinyl. When two adjacent substituents on Ring C are taken together to form a fused ring, Ring C is contained in a bicyclic ring system. Preferred fused rings include a benzo or pyrido ring. Such rings preferably are fused at ortho and meta positions of Ring C. Examples of preferred bicyclic Ring C systems include naphthyl and isoquinolinyl. Preferred R1 groups include -halo, an optionally substituted Ci-e aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, ,-CO2R6, -CONH2/ -NHCOR6, -OC(O)NH2, or -NHS02RG. When R1 is an optionally substituted Ca-6 aliphatic group, the most preferred optional substituents are halogen. Examples of preferred R1 groups include -CF3, -Cl, -F," -CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2CH3, -CH3, -CF2CH3, cyclohexyl, t-butyl, isopropyl, cyclopropyl, -C=CH, -C=C-CH3, -SO2CH3, -SO2NH2, -N(CH3)2, -CO2CH3/ -CONH2, -NHCOCH3/ -OC(O)NH2, -NHSO2CH3/ and -OCF3. On Ring C preferred R5 substituents, when present, include -halo, -CN, -N02/ -N(R4)2, optionally substituted Cx-6 aliphatic group, -OR, -C(O)R, -CO2R,' -CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4) SO2R. More preferred R5 substituents include -Cl, -F, -CN, -CF3, -NH2, -NH(CH2-4 aliphatic), -N(C1-4 aliphatic)2 -O(C1-4 aliphatic), C1-4 aliphatic, and -CO2(C1-4 aliphatic). Examples of such preferred R5 substituents include -Cl, -F, -CN, -CF3, -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, and -CO2Et. When G is Ring D, preferred formula VI Ring D monocyclic rings include substituted and unsubstituted phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings. When two adjacent substituents on Ring D are taken together to form a fused ring, the Ring D system is bicyclic Preferred formula VT Ring D bicyclic rings include 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro- 1H- isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, guinolinyl, and naphthyl. Examples of more preferred bicyclic Ring D systems include naphthyl and isoquinolinyl. Preferred substituents on formula VT Ring D include one or more of the following: halo, oxo, CN, -N02, -N(R4)2, -CO2R, -C0NH(R4), -N(R4)COR, -SO2N(R4)2/ -N(R4)SO2R, -SR, -OR, -C(O)R, or substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. More preferred Ring D substituents include -halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1_6 aliphatic. Examples of Ring D substituents include -OH, phenyl, methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, C=CH, Cl, Br, F, I, NH2, C(O)CH3, i-propyl, tert-butyl, SEt, OMe, N(Me)2, methylene dioxy, and ethylene dioxy. Preferred formula VI compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is selected from a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring, and R1 is -halo, an optionally substituted C1_6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; or Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4- tetrahydroisoguinolinyl, 1,2,3,4-tetrahydroquinolinyl, 2,3 -dihydro- 1H-isoindolyl, 2,3-dihydro- 1H-indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; (b) Ry is T-R3', wherein T is a valence bond or a methylene; and (c) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1_6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring. More preferred compounds of formula VT have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1_6 haloaliphatic group, a C1_6 aliphatic group, phenyl, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisbguinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3- dihydro- 1H- isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or naphthyl; (b) Ry is T-R3', wherein T is a valence bond or a methylene and R3 is an optionally substituted group selected from C1_6 aliphatic, C3-6 carbocyclyl, C6-10 aryl, a heteroaryl- ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; (c) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, or a C1_6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and (d) Ring D is substituted by oxo or R5, wherein each R5 is independently selected from -halo, -CN, -NO2, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, or -N(R4)S02R. Even more preferred compounds of formula VI have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ry is T-R3', wherein T is a valence bond or a methylene and R3' is an optionally substituted group selected from C1-4 aliphatic, C3.6 carbocyclyl, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring; (b) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-4 aliphatic group optionally substituted with halogen, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, isoquinolinyl, guinolinyl, or naphthyl; (c) R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -d-4 haloalkyl, -N02, -O(C1-4 alkyl) , -CO2(C1-4 alkyl) , -CN, -SO2(C1-4 alkyl) , -SO2NH2, -0C(O)NH2, -NH2SO2(C1-4 alkyl) , -NHC(O) (C1_4 alkyl) , -C(O)NH2, or -CO (C1-4 alkyl) , wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group,- and (d) Ring D is substituted by oxo or R5, wherein each Rs is independently selected from -C1, -F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -0(C1-4 aliphatic) , C1_4 aliphatic, and -CO2(C1-4 aliphatic). Another embodiment of this invention relates to compounds of formula VXa: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring CU are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; R1 is selected from -halo, -CN, -N02, T-V-Re, phenyl, 5-6 membered heteroaryl ring, 5-6 menibered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R8, said C1_6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms _form said ring fused to Ring C; T is a valence bond or a C1_4 alkylidene chain; R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4 ; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R on the same nitrogen are taken together to form a 5-8. membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2/ -C=NN(R4)2, -C=N-OR, -N (R4) CON (R4) -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(-O)N(R4) 2, or Rs and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; V is -0-, -S-, -SO-, -S02-, -N(R6)SO2-# -SO2N(R6)-, -N(R6)-, -CO-, -C02-, -N(R6)CO-, -N(RS) C(O) 0-, -N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(R6)N(R6) -, -C(O)N(R6)-, -OC(O)N(R6)-,' -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(RS)2SO2N(R6)-, -C (R6) 2N(R6)-, -C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN (R6) - , -C(R6)=N-O-, -C(R6)2N{Re)N(R6)-, -C(R6) 2N(R6) SO2N(R6) - , or -C(R6)2N(R6)CON(R6)-; W is -C(R6)2O-, -C(R6)2S-, -C(R6)2S0-, -C(R6)2SO2-, -C{R6)2SO2N(RS)-, -C(R6)2N(R6)-, -CO-, -C02-, -C(R6)OC(O)-, -C(R6)OC(0)N(R6)-, -C (R6)2N(R6) CO-, -C{R6)2N(R6)C(O)O-, -C(R6)=NN(R6)-, -C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C(R6)2N(R6)SO2N(R6)-, -C(R6)2N(R6)CON(R6)-/ or -CON{R6)-; each R6 is independently selected from hydrogen, an optionally substituted C1-4 aliphatic group, or two Rs groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; and each R8 is independently selected from an optionally substituted C1-4 aliphatic group, -OR6, -SR6, -COR6, -SO2R6, -N(R6)2, -N(R6)N(R6)2, rCN, -N02, -CON(R6)2, or -CO2R6. Preferred rings formed by the R2 and R2' groups of formula Via include benzo, pyrido, pyrimido, and a partially unsaturated 6-membered carbocyclo ring. These are exemplified in the following formula VIa compounds having a pyrazole-containing bicyclic ring system: Preferred substituents on the R2/R2 fused ring include one or more of the following: -halo, -N(R4)2, -C1-4 alkyl, -C1.4 haloalkyl, -NO2, -O(C1-4 alkyl) , -CO2(C1_4 alkyl) , -CN, -S02 (C1-4 alkyl) , -SO2NH2, -OC(O)NH2, -NH2SO2(C1.4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(O)NH2, and -CO(C1-4 alkyl), wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group. Preferably, the (C1-4 alkyl) group is methyl. When G is Ring C, preferred formula VIa Ring C groups are phenyl and pyridinyl. When two adjacent substituents on Ring C are taken together to form a fused ring Ring C is contained in a bicyclic ring system. Preferred fused rings include a benzo or pyrido ring. Such rings preferably are fused at ortho and meta positions of Ring C. Examples of preferred bicyclic Ring C systems include naphthyl and isoquinolinyl. Preferred R1 groups include -halo, an optionally substituted C1-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(Rs)2, -CO2R6, -C0NH2, -NHCOR6, -0C(0)NH2, or -NHSO2R6. When R1 is an optionally substituted C1-6 aliphatic group, the most preferred optional substituents are halogen. Examples of preferred R1 groups include -CF3, -C1, -F, -CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2OCH3, -CH3, -CF2OCH3, cyclohexyl, t-butyl, isopropyl, cyclopropyl, -CsCH, -C=C-OCH3, -SO2CH3/ -SO2NH2, -N(CH3)2, -CO2CH3, -CONH2, -NHCOCH3, -OC(O)NH2, -NHSO2CH3, and -OCF3. On Ring C preferred Rs substituents, when present, include -halo, -CN, -N02, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, - CONH (R4) , -N (R4) COR, - SO2N (R4) 2, and -N (R4) SO2R. More preferred R5 substituents include -Cl, -F, -CN, -CF3, -NH2, -NH(OCH3.4 aliphatic) , -N(C1-4- aliphatic)2, -o(C1-4 aliphatic), C3..4 aliphatic, and -CO2(C1-4 aliphatic). Examples of such preferred Rs substituents include -Cl, -F, -CN, -CF3 -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, and -CO2Et. When G is Ring D, preferred formula VIa Ring D monocyclic rings include substituted and unsubstituted phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings. When two adjacent substituents on Ring D are taken together to form a fused ring, the Ring D system is bicyclic. Preferred formula VIa Ring D bicyclic rings include 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, quinolinyl, and naphthyl. Examples of more preferred bicyclic Ring D systems include naphthyl and isoquinolinyl. Preferred substituents on the formula Via Ring D include one or more of the following: halo, oxo, CN, -N02, -N(R4)2, -CO2R, -CONH(R4), -N(R4)C0R, -SO2N(R4)2, -N(R)S02R, -SR, -OR, -C(0)R, or substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-io axyl, or C1-6 aliphatic. More preferred Ring D substituents include -halo, -CN, -oxo, -SR, -OR, -N(R )2/ -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C2.e aliphatic. Examples of Ring D substituents include -OH, phenyl, methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, OsCH, C1, Br, F, 2, NH2, C(O)CH3, i-propyl, tetr-butyl, SEt, OMe, N(Me)2, methylene dioxy, and ethylene dioxy. Preferred formula VIa compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or. isoquinolinyl ring, and R1 is -halo, an. optionally substituted C1_6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SOaNH2, -N(K6)2, -CO2RS, -CONH2, -NHCOR, -OC{O)NH2, or -NHSO2R6; or Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyi, 2,3-dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; and (b) R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6- membered carbocyclo ring. More preferred compounds of formula VIa have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-e haloaliphatic group, a C1-6 aliphatic group, phenyl, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4 - tetrahydroisoquinolinyl, 1,2,3,4- tetrahydxoquiholinyl, 2,3 -dihydro- Iff- isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or naphthyl; (b) R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2, -C1_4 alkyl, -Ca-4 haloalkyl, -N02, -O(C1-4 alkyl) , -C02 (Ca-4 alkyl) , -CN, -S02(C1.4 alkyl) , -SOsNHa, -0C(O)NH2, -NH2S02 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl), -C(O)NH2/ and - CO (C1-4 alkyl), wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group; and (c) Ring D is substituted by oxo or Rs, wherein each Rs is independently selected from -halo, -CN, -N02, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -C0NH{R4), -N(R4)COR, -SO2N(R4)2, or -N(R4)SO2R. Even more preferred compounds of formula VIa have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-4 aliphatic group optionally substituted with halogen, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-t etrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, isoquinolinyl, quinolinyl, or naphthyl; (b) R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -C1-4 haloalkyl, -N02, -0(d.4 alkyl) , -C02 (C1 alkyl) , -CN, -SO2(C1-4 alkyl) , -SO2NH2, -OC(O)NH2/ -NH2SO2 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(O)NH2, or -C0(Ci.4 alkyl) , wherein the (Ci_4 alkyl) is a straight, branched, or cyclic alkyl group; and (d) Ring D is substituted by oxo or Rs, wherein each R5 is independently selected from -Cl, -F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -o(C1-4 aliphatic), C1-4 aliphatic, and -CO2(C1.4 aliphatic). Representative compounds of formula VI and XVa are set forth in Table 5 below. In another embodiment, this invention provides a composition comprising a compound of formula VI or VIa and a pharmaceutically acceptable carrier. One aspect of this invention relates to a method of inhibiting GSK-3 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. Another aspect relates to a method of treating a disease that is alleviated by treatment with a GSK-3 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. Another aspect relates to a method of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. This method is especially useful for diabetic patients. Another aspect relates to a method of inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. This method is especially useful in halting or slowing the progression of Alzheimer's disease. Another aspect relates to a method of inhibiting the phosphorylation of p-catenin in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. This method is especially useful for treating schizophrenia. One aspect of this invention relates to a method of inhibiting Aurora activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. Another aspect relates to a method of treating a disease that is alleviated by treatment with an Aurora inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. This method is especially useful for treating cancer, such as colon, ovarian, and breast cancer. One aspect of this invention relates to a method of inhibiting CDK-2 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. Another aspect relates to a method of treating a disease that is alleviated by treatment with a CDK-2 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VI or VIa. This method is especially useful for treating cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis, alopecia, and autoimmune diseases such as rheumatoid arthritis. Another method relates to inhibiting GSK-3, Aurora, or CDK-2 activity in a biological sample, which method comprises contacting the biological sample with the GSK-3 or Aurora inhibitor of formula VI or VIa, or a pharmaceutical composition thereof, in an amount effective to inhibit GSK-3, Aurora or CDK-2. Each of the aforementioned methods directed, to the inhibition of GSK-3, Aurora or CDK-2, or the treatment of a disease alleviated thereby, is preferably carried out with a preferred compound of formula VI or VIa, as described above. Another embodiment of this invention relates to compounds of formula VII. or a pharmaceutically acceptable derivative or prodrug thereof, wherein: G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-5 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; Ring D is a 5-7. membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -Rs is hydrogen at each ortho carbon position of Ring D; R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R5, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Ry is hydrogen or T-R3"; T is a valence bond, hydrogen, or a C1-4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4; R3* is selected from an optionally substituted group selected from C3-10 carbocyclyl, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -C0N(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)C0R, -N(R4)CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-0R, -N(R4) CON(R4) 2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2, or R5 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; V is -0-, -S-, -SO-, -S02-, -N(R6)SO2-, -SO2N(R6)-, -N(R6)-, -CO-, -C02-, -N(R6)CO-, -N(R6) C(0) 0-, -N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(R6)N(R6) -, -C(0)N(R6)-, -OC(O)N(R6)-, -C(RS)2O-, -C(Re)2S-, -C(Re)2SO-, -C(R6)2SO2-, -C(R6)2S02N(R6)-, -C(R6) 2N(R6) -, -C(R6)2N(R6)C(0)-, -C(R6)2N(R6)C(O)O-, -C(R6) =NN(R6)-, -C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C (R6) 2N (R6) SO2N (R6) - , or -C (Rs) 2N (Re) CON (R6) - ; W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -C02-, -C(RS)OC(O)-, -C(R6)0C(0)N(R6)-, -C (R6) 2N(RC) CO-, -C(R6)2N(RS)C(O)O-, -C(R6)=NN(R6)-, -C(R6)=N-O-, -C (R6) 2N (Re) N (R6) - , -C(R6) 2N (R6) S02N (R6) -, -C(RS)2N(RG)CON(R6)-, or -CON(R6)-; each R6 is independently selected from hydrogen, an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; each R8 is independently selected from an optionally substituted C1-4 aliphatic group, -OR6, -SR6, -COR6, -SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -C0N(R6)2, or -CO2R6; and R9 is selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(0)R, -SO2R, -SR, -N(R4)2/ -CON(R4)2, -SO2N(R4)2/ -OC(=0)R, -N(R4)COR, -N(R4) C02 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N(R4) SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2. Preferred Ry groups of formula VII include T-R3" wherein T is a valence bond or a methylene. Preferred R3" groups include an optionally substituted group selected from C3-6 carbocyclyl, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring. Examples of preferred Ry include 2-pyridyl, 4-pyridyl, piperidinyl, cyclopropyl, and an optionally substituted phenyl such as phenyl or halo-substituted phenyl. The R2 and R2' groups of formula VII may be taken together to form a fused ring, thus providing a bicyclic ring system containing a pyrazole ring. Preferred fused rings include benzo, pyrido, pyrimido, and a partially \msaturated 6-membered carbocyclo ring. These are exemplified in the following formula VTI . compounds having a pyrazole-containing bicyclic ring system: Preferred substituents on the R2/R2' fused ring include one or more of the following: -halo, -N(R4)2, -C1-4 alkyl, -C1-4 naloalkyl, -NO2, -O (C1-4 alkyl) , -CO2(C1-4 alkyl), -CN, -SO2(C1-4 alkyl) , -SO2NH2, -OC(O)NH2, -NH2SO2(C1-4 alkyl), -NHC(O) (C1-4 alkyl) , -C(O)NH2, and -CO(C1-4 alkyl), wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group. Preferably, the (C1-4 alkyl) group is methyl. When the pyrazole ring system of formula VTI. is monocyclic, preferred R2 groups include hydrogen, C1-4 aliphatic, alkoxycarbonyl, (un) substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N- heterocyclyDcarbonyl. Examples of such preferred R2 substituents include methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CT2CH2NHCOOC (CH3) 3, CONHCH(C3I3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, COKHCH2Ph, CONH(cyclohexyl) , CON(Et)2, CON(CH3) CH2Ph, CONH(n-C3H7) , CON(Et)CH2CH2CH3, CONHCH2CH (CH3)2, CON(n-C3H7)2, CO(3- methoxymethylpyrrolidin-1-yl), CONH(3-tolyl), CONH(4- tolyl) , CONHCH3, CO(morpholin-l-yl) , CO(4-methylpiperazin- 1-yl) , CONHCH2CH2OH, CONH2/ and CO(piperidin-1-yl) . A preferred R2' group is hydrogen. When G is Ring C, preferred formula VTI Ring C groups are phenyl and pyridinyl. When two adjacent substituents on Ring C are taken together to form a fused ring, Ring C is contained in a bicyclic ring system. Preferred fused rings include a benzo or pyrido ring. Such rings preferably are fused at ortho and meta positions of Ring C. Examples of preferred bicyclic Ring C systems include naphthyl and isoquinolinyl. Preferred R1 groups include -halo, an optionally substituted Ca-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2/ -N(R6)2, -CO3R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2RS. When R1 is an optionally substituted C1-6 aliphatic group, the most preferred optional substituents are halogen. Examples of preferred R1 groups include -CF3, -Cl, -F, -CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2CH3, -CH3, -CF2CH3, cyclohexyl, t-butyl, isopropyl, cyclopropyl, -CsCH, -C=C-CH3, -SO2CH3, -SO2NH2, -N{CH3)2, -CO2CH3, -CONH2, -NHCOCH3, -OC(O)NH2, -NHSO2CH3, and -OCF3.. On Ring C preferred R5 substituents, when present, include -halo, -CN, -NO2, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4) SO2R. More preferred R5 substituents include -Cl, -F, -CN, -CF3, -NH2, -HH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -O(C1-4 aliphatic), C1-4 aliphatic, and -CO2(C1-4 aliphatic). Examples of such preferred R5 substituents include -Cl, -F, -CN, -CF3, -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, and -CO2Et. When G is Ring D, preferred formula VII Ring D monocyclic rings include substituted and unsubstituted phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings. When two adjacent substituents on Ring D are taken together to form a fused ring, the Ring D system is bicydic. Preferred formula VTI Ring D bicyclic rings include 1,2,3,4-tetrahydroisoguinolinyl, 1,2,3,4- tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, quinolinyl, and naphthyl. Examples of more preferred bicyclic Ring D systems include naphthyl and isoquinolinyl. Preferred substituents on Ring D include one or more of the following: halo, oxo, CN, -N02, -N(R4)2, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. More preferred Ring D substituents include -halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. Examples of Ring D substituents include -OH, phenyl, methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, OCH, Cl, Br, F, I, NH2, C(O)CH3, i-propyl, tert-butyl, SEt, OMe, N(Me)2, methylene dioxy, and ethylene dioxy. Preferred formula VII compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring, and R1 is -halo, an optionally substituted C1-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -C0aR6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; or Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, 2,3-dihydro- IH-isoindolyl, 2,3 -dihydro- 1H- indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; (b) Ry is T-R3", wherein T is a valence bond or a methylene; and (c) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring. (b) More preferred compounds of formula VII have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic group, phenyl, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3- dihydro-lH-indolyl, isoguinolinyl, quinolinyl, or naphthyl; (b) Ry is T-R3", wherein T is a valence bond or a methylene and R3" is an optionally substituted group selected from C3-6 carbocyclyl, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring; (c) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, or a C1-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and (d) Ring D is substituted by oxo or R5, wherein each R5 is independently selected from -halo, -CN, -N02, -N{R4)a, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, or -N(R4)SO2R. Even more preferred compounds of formula VII have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ry is T-R3", wherein T is a valence bond or a methylene and R3" is an optionally substituted group selected from phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring; (b) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-4 aliphatic group optionally substituted with halogen, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisoguinolinyl, 1,2,3,4- tetrahydroquinolinyl, isoguinolinyl, quinolinyl, or naphthyl; (c) R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -C1-4 haloalkyl, -N02, -O(C1-4 alkyl) , -CO2 (C1-4 alkyl) , -CN, - S02 (C1-4 alkyl) , - SO2NH2, - OC (0) NH2, -NH2SO2 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(O)NH2, or -CO(C1-4 alkyl) , wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group; and (d) Ring D is substituted by oxo or R5, wherein each R5 is independently selected from -Cl, -F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -O(C1-4 aliphatic), C1-4 aliphatic, and -CO2(C1-4 aliphatic). Representative compounds of formula VII are set forth in Table 6 below. In another embodiment, this invention provides a composition comprising a compound of formula VTI and a pharmaceutically acceptable carrier. One aspect of this invention relates to a method of inhibiting GSK-3 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula VII. Another aspect relates to a method of treating a disease that is alleviated by treatment with a GSK-3 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VII. Another aspect relates to a method of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VTI. This method is especially useful for diabetic patients. Another aspect relates to a method of inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VII.' This method is especially useful in halting or slowing the progression of Alzheimer's disease. Another aspect relates to a method of inhibiting the phosphorylation of ?-catenin in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VTI. This method is especially useful for treating schizophrenia. One aspect of this invention relates to a method of inhibiting Aurora activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula VT1. Another aspect relates to a method of treating a disease that is alleviated by treatment with an Aurora inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VII. This method is especially useful for treating cancer, such as colon, ovarian, and breast cancer. One aspect of this invention relates to a . method of inhibiting CDK-2 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula VII. Another aspect relates to a method of treating a disease that is alleviated by treatment with a CDK-2 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VII. This method is especially useful for treating cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis, alopecia, and autoimmune diseases such as rheumatoid arthritis. Another method relates to inhibiting GSK-3, Aurora, or CDK-2 activity in a biological sample, which method comprises contacting the biological sample with the GSK-3 or Aurora inhibitor of formula VII, or a pharmaceutical composition thereof, in an amount effective to inhibit GSK-3, Aurora or CDK-2. Each of the aforementioned methods directed to the inhibition of GSK-3, Aurora or CDK-2, or the treatment of a disease alleviated thereby, is preferably carried out with a preferred compound of formula VII, as described above. Another embodiment of this invention relates to compounds of formula VIII: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: Z1 is N or CR9, Z2 is N or CH, and Z3 is N or CRX, provided that one of Z1 and Z3 is nitrogen; G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is . substituted at any substitutable ring carbon by halo, oxo, or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -Rs is hydrogen at each ortho carbon position of Ring D; R1 is. selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -RB, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Rx is T-R3; T is a valence bond or a C1-4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -C0CH2C0R, -NO2, -CN, -S(O)R, -S(O)2R, -SR, -N(R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7)CO2 (optionally substituted C1-6 aliphatic), -N(R4)N(R4)2, -C=NN(R4)2, -O=N-0R, -N(R7) CON(R7)2, -N(R7)SO2N(R7)2, -N(R4)SO2R, or -OC(=O)N(R7)2; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted d1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SOaR, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) CO2 (optionally substituted C1-6 aliphatic), -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R4) CON (R4) 2, -N(R4)SO2N(R4)2l. -N(R4)SO2R, or -OC(=O)N(R4)2, or Rs and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; V is -O-, -S-, -SO-, -SOa-, -N(R)SO2-, -S02N(RG)-, -N(R6)-, -CO-, -COa-, -N(R6)CO-, -N(R6)C(O)O-, -N(R6)CON(R6)-, • -N(R6)SO2N(R6)-, -N(R6)N(RS) - , -C(O)N(R6)-, -OC(O)N(R6)-, -C(Re)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(RS)2SO2N(R6)-, -C (Rs) 2N (Rfi) - . -C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN(R6) - , -C(RS)=N-O-, -C(R6)2N(R6)N(R6)-, -C (R6) 2N(R6) SO2N(Re) - , or -C(R6)2N(R6)CON(R6)-; W is -C(RS)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(Re)-, -C(R6)2N(R6)-, -CO-, -CO2-, -C(R6)OC(O)-, -C(R6)OC(O)N(R6)-, -C (R6) 2N(R6) CO- , -C(R6)2N(RS)C(O)O-, -C(R€)=KN(R6)-, -C(RS)=N-O-, -C(R6)2N(R6)N(R6)-, -C(R6)2N(R6)SO2N(R6)-, -C(R6)2N(RS)CON(R6)-, or -CON(R6)-; each R6 is independently selected from hydrogen, an optionally substituted Ci.4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with' the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; each R8 is independently selected from an optionally substituted Ca-4 aliphatic group, -OR6, -SR6, -COR6, -SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -NO2, -CON(R6)2/ or -CO2R6; and R9 is selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NOa, -CN, -S(O)R, -SO2R, -SR, -N(R)2, -CON(R)2, -SO2N(R4)2, -OC(=O)R, -N(R4)C0R, -N(R4) CO2 (optionally substituted Ca.6 aliphatic) , -N(R)W(R)2, -C=NN{R4)2, -C=N-OR, -N(R)CON(R4)2/ -N(R4) S02N(R4) 2, -N(R)SO2R, or -OC(=O)N(R4}2. Accordingly, the present invention relates to compounds of formula Villa, Vlllb, VTIIc and VHId as sb.own below: VIIIa VTIIb VIIIc VTIId Preferred Rx groups of formula VIII include T-R3 wherein T is a valence bond or a methylene and R3 is CN, -R, or -OR. When R3 is -R, preferred R3 groups include an optionally substituted group selected from C1-6 aliphatic, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring. When R3 is -OR, preferred R groups include an optionally substituted group C1-6 aliphatic group such as alkyl- or dialkylaminoalkyl and aminoalkyl. Examples of preferred Rx include acetamido, CN, piperidinyl, piperazinyl, phenyl, pyridinyl, imidazol-1-yl, imidazol- 2-yl, cyclohexyl, cyclopropyl, methyl, ethyl, isopropyl, t-butyl, NH2CH2CH2NH, and NH2CH2CH2O. Preferred R9 groups of formula VIII, when present, include R, OR, and N(R4)2. Examples of preferred R9 include methyl, ethyl, NH2, NH2CH2CH2NH, N(CH3)2CH2CH2NH, N{CH3)2CH2CH2O, (piperidin-l-yl)CH2CH2O, and NH2CH2CH2O. The R2 and R2' groups of formula VIII may be taken together to form a fused ring, thus providing a bicyclic ring system containing a pyrazole ring. Preferred fused rings include benzo, pyrido, pyrimido, and a partially unsaturated 6-membered carbocyclo ring. These are exemplified in the following formula VTII compounds having a pyrazole-containing bicyclic ring system: Preferred substituents on the formula VIII R2/R2' fused ring include one or more of the following: -halo, -N(R4)a, -C1-4 alkyl, -d-4 haloalkyl, -NO2, -O(Cd-4 alkyl) , -CO2(C1-4, alkyl) , -CN, -S02 (C1-4 alkyl) , -SO2NH2, -OC (O)NH2, -NH2SO2(C1-4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(o)NH2. and -CO(C1-4 alkyl) , wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group. Preferably, the (d-4 alkyl) group is methyl. When the pyrazole ring system of formula VIII is monocyclic, preferred R2 groups include hydrogen, d-4 aliphatic, alkoxycarbonyl, (un) substituted phenyl, hydxoxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N- heterocyclyl)carbonyl. Examples of such preferred R2 substituents include methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, C02H, CO2CH3, CH2OH, CR2OCK3, CHfeCEfeCHzOH, CH2CH2CH2OCH3, C3I2CH2CH2OC3J2Ph, CH2CH2CH2NH2 / CH2CH2CH2NHCOOC (CH3)3, COKHCH(CH3)2, CONHCH2CH=CH2, CONHGH2CH2OCH3/ CONHCH2Ph, CONH(cyclohexyl), CON(Et)2, CON(CH3) CH2Ph, CONH(n-C3H7) , CON(Et)CH2CH2CH3, CONHCH2CH (CH3) a, CON(n-C3H7) 2, C0(3- methoxymethylpyrrolidin-1-yl), CONH(3-tolyl) , CONH(4- tolyl) , CONHCH3, CO(morpholin-1-yl) , C0(4-methylpiperazin- 1-yl) , CONHCH2CH2OH, CONH2, and CO(piperidin-l-yl) . A preferred R2' group is hydrogen. When G is Ring C, preferred formula VIII Ring C groups are phenyl and pyridinyl. When two adjacent substituents on Ring C are taken together to form a fused ring, Ring c is contained in a bicyclic ring system. Preferred fused rings include a benzo or pyxido ring. Such rings preferably are fused at ortho and meta positions of Ring C. Examples of preferred bicyclic Ring C systems include naphthyl and isoquinolinyl. Preferred R1 groups include -halo, an optionally substituted C1-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6. When R1 is an optionally substituted C1-6 aliphatic group, the most preferred optional substituents are halogen. Examples of preferred R1 groups include -CF3, -Cl, -F, -CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2CH3, -CH3, -CF2CH3, cyclohexyl, t-butyl, isopropyl, cydopropyl, -OsCH, -CsC-CH3/ -SO2CH3, -SOaNH2, -N(CH3)2, -CO2CH3, -CONH2, -NHCOCH3, -OC(O)NH2f -NHSO2CH3, and -OCF3. On Ring C preferred R5 substituents, when present, include -halo, -CN, -N02, -N(R)2/ optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -C0NH(R4) , -N(R)COR, -S02N(R4)2, and -N(R)SO2R. More preferred R5 substituents include -Cl, -F, -.CN, -CF3, -NH2, -NH(Ci-4 aliphatic), -N(Ci_« aliphatic)2, -0(Ci-4 aliphatic), C^ aliphatic, and -CO2(d.4 aliphatic). Examples of such preferred Rs substituents include -Cl, -F, -CN, -CF3, -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, and -CO2Et. When G is Ring D, preferred formula VIII Ring D monocyclic rings include substituted and unsubstituted phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings. When two adjacent substituents on Ring D are taken together to form a fused ring, the Ring D system is bicyclic. Preferred formula VTII Ring D bicyclic rings include 1,2,3,4-tetrahydroisoquinplinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro-1H- isoindolyl, 2,3- dihydro-ltf-indolyl, isoquinolinyl, quinolinyl, and naphthyl. Examples of more preferred bicyclic Ring D systems include naphthyl and isoquinolinyl. Preferred R5 eubstituents on Ring D of formula VIII include halo, oxo, CN, -N02, -N{R4)2/ -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-i0 aryl, or Ci-6 aliphatic. More preferred R* substituents include -halo, -C3ST, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-io aryl, or C^g aliphatic. Examples of Ring D substituents include -OH, phenyl, methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, OsCH, Cl, Br, F, I, NH2, C(O)CH3, i-propyl, Cert-butyl, SEt, OMe, N(Me)2, methylene dioxy, and ethylene dioxy. Preferred formula VIII compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring, and R1 is -halo, an optionally substituted Ci-e aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(Re)2, -CO2R6, -C0NH2, -NHCORe, -OC(O)NH2, or -NHSO2R6; or Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; (b) Rx is T-R3 wherein T is a valence bond or a methylene; and (c) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring. More preferred compounds of formula VIII have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic group, phenyl, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4- tetrahydroisoguinolinyl, 1,2,3,4- tetrahydxoquinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or naphthyl; . (b) Rx is T-R3 wherein T is a valence bond or a methylene and R3 is CN, -R or -OR; (c) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, or a C1-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and (d) each R5 is independently selected from -halo, -CN, -NO2, -N(R4)2, optionally substituted CC1-6 (b) aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4) , -N(R4)COR, -SO2N(R4)2, or -N(R4)SO2R. Even more preferred compounds of formula VTII have one or more, and more preferably all, of the features selected from the group consisting of: (a) Rx is T-R3 wherein T is a valence bond or a methylene and R3 is -R or -OR wherein R is an optionally substituted group selected from C1-6 aliphatic, phehyl, or a 5-6 membered heteroaryl or heterocyclyl ring; (b) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-4 aliphatic group optionally substituted with halogen, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, isoquinolinyl, quinolinyl, or naphthyl; (c) R2 and R2' are taken together with their • intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -C1-4 haloalkyl, -NO2, ~O(C1-4 alkyl), -CO2 (C1-4 alkyl) , -CN, -SO2 (C1-4 alkyl) , -SO2NH2, -OC(O)NH2, -NH2SO2 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(O)NH2, or -CO (C1-4 alkyl) , wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group; (d) each R5 is independently selected from -Cl, -F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -0(C1-4 aliphatic) , C1-4 aliphatic, and -CO2(C1-4 aliphatic) ; and (c) In another embodiment, this invention provides a composition comprising a compound of formula VIII and a pharmaceutically acceptable carrier. One aspect of this invention relates to a method of inhibiting GSK-3 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula VIII. Another aspect relates to a method of treating a disease that is alleviated by treatment with a GSK-3 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VIII. Another aspect relates to a method of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VIII. This method is especially useful for diabetic patients. Another aspect relates to a method of inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VIII. This method is especially useful in halting or slowing the progression of Alzheimer's disease. Another aspect relates to a method of inhibiting the phosphorylation of ?-catenin in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula VIII. This method is especially useful for treating schizophrenia. One aspect of this invention relates to a method of inhibiting Aurora activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula vIII. Another aspect relates to a method of treating a disease that is alleviated by treatment with an Aurora inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VIII. This method is especially useful for treating cancer, such as colon, ovarian, and breast cancer. 3 One aspect of this invention relates to a method of inhibiting CDK-2 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula VIII. ) Another aspect relates to a method of treating a disease that is alleviated by treatment with a CDK-2 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula VIII. This method is especially useful for treating cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis, alopecia, and autoimmune diseases such as rheumatoid arthritis. Another method relates to inhibiting GSK-3, Aurora, or CDK-2 activity in a biological sample, which method comprises contacting the biological sample with the GSK-3 or Aurora inhibitor of formula VIII, or a pharmaceutical composition thereof, in an amount effective to inhibit GSK-3, Aurora or CDK-2. Each of the aforementioned methods directed to the inhibition of GSK-3, Aurora or CDK-2, or the . treatment of a disease alleviated thereby, is preferably ) carried out with a preferred compound of formula VIII, as described above. The above formula I compounds contain a pyrazole ring bearing the R2 and R2' substituents. In their search for further inhibitors of the protein kinases GSK and Aurora, applicants sought to replace the pyrazole moiety of formula I with other heteroaromatic rings. One of the more effective pyrazole ring replacements was found to be a triazole ring. Inhibitors having this triazole ring are otherwise structurally similar to the formula I compounds and are represented by the general formula IX: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: Z1 is nitrogen or OR9 and Z2 is nitrogen or CH, provided that at least one of Z1 and Z2 is nitrogen; G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; Ring D is a 5-7 membered monocyclic ring or 8-10 tnembered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6 merabered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -RB, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 merabered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3, and any substitutable nitrogen on said ring formed by Rx and Ry is substituted by R4; T is a valence bond or a C1-4 alkylidene chain; R2 is -R or -T-W-R6; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocydyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7): or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring,- each R5 is independently selected from -R, halo, -OR, each R6 is independently selected from hydrogen, an optionally substituted C1-4 aliphatic gxoup, or two R6 groups on the same nitrogen atom are taken together - with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; each R8 is independently selected from an optionally Compounds of formula IX may exist in alternative tautomeric forms, as in tautomers 1-3 shown below. Unless otherwise indicated, the representation of any of these tautomers is meant to include the other two. The Rx and Ry groups of formula IX may be taken together to form a fused ring, providing a bicyclic ring system containing Ring A. Preferred Rx/Ry rings include a 5-, 6-, 7-, or 8-membered unsaturated or partially unsaturated ring having 0-2 heteroatoms, wherein said Rx/Ry ring is optionally substituted. Examples of Ring A systems are shown below by compounds IX-A through IX-DD, wherein Z1 is nitrogen or C(R9) and Z2 is nitrogen or C(H). In the monocyclic Ring A system of formula IX, preferred Rx groups include hydrogen, alkyl- or dialkylamino, acetamido, or a C1-4 aliphatic group such as methyl, ethyl, cyclopropyl, .isopropyl or t-butyl. Preferred Ry groups, when present, include T-R3 wherein T is a valence bond or a methylene, and R3 is -R, -N(R4)2, or -OR. Examples of preferred RY include 2-pyridyl, 4- pyridyl, piperidinyl, methyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or dialkylamino, acetamido, optionally substituted phenyl such as phenyl or halo- substituted phenyl, and methoxymethyl. In the bicyclic Ring A system of formula IX, the ring formed by Rx and Ry taken together may be substituted or unsubstituted. Suitable substituents include -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted C1-6 aliphatic), -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2, wherein R and R4 are as defined above. Preferred Rx/Ry ring substituents include -halo, -R, -OR, -COR, -CO2R, -CON(R4)2, -CN, or -N(R4)2 wherein R is an optionally substituted C1-6 aliphatic group. Preferred R2 groups of formula IX include hydrogen, C1-4 aliphatic, alkoxycarbonyl, (un) substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N- heterocyclyl)carbonyl. Examples of such preferred R2 substituents include methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, C3J2OCH3, CH2CH2CH2OH/ CH2CH2CH2OCH3, CHzCHaCHaOCHaPh, CH2CH2CH2NH2, CH2CHaCH2NHCOOC(CH3) 3) CONHCH(C3J3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl) , CON(Et)2, CON(CH3) CH2Ph, CONH(n-C3H7) , CON(Et)CH2CH2CH3, CONHCH2CH (CH3) 2, CON(n-C3H7) 2, C0(3- methoxymethylpyrrolidin-1-yl) , CONH(3-tolyl) , C0NH(4- tolyl) , CONHCH3, CO(morpholin-l-yl), C0(4-methylpiperazin- 1-yl) , CONHCH2CH2OH, CONH2, and CO (piperidin-1-yl) . A more preferred R2 group for formula IX compounds is hydrogen. An embodiment that is particularly useful for treating GSK3-mediated diseases relates to compounds of formula X wherein, ring A is a pyrimidine ring: or a pharmaceutically acceptable derivative or prodrug thereof, wherein; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridaziny1, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; R1 is selected from -halo, -CSS, -N02, T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R8, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3, and any substitutable nitrogen on said ring formed by Rx and Ry is substituted by R4; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, each R6 is independently selected from hydrogen, an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-S membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; and each R8 is independently selected from an optionally substituted C1-4 aliphatic group, -OR6, -SR6, -COR6, -SO3R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or -CO2R6. Compounds of formula X are structurally similar to compounds of formula II except for the replacement of the pyrazole ring moiety by the triazole ring moiety. Preferred R2, Rx, Ry and Ring C groups of formula X are as described above for the formula II compounds. Preferred formula X compounds have one or more, and more preferably- all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring; (b) Rx is hydrogen or C1-4 aliphatic and Ry is T- R3, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted 5-7 membered unsaturated or partially unsaturated ring having 0-2 ring nitrogens ,- (c) R1 is -halo, an optionally substituted C1-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6, -CONH2, -NHCOR6, -0C(0)NH2, or -NHSO2Re; and (d) R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1-6 aliphatic group. More preferred compounds of formula X have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring; (b) R* is hydrogen or methyl and Ry is -R, N{R4)2, or -OR, or Rx and Ry are taken together with their intervening atoms to form a benzo ring or a 5-7 membered carbocyclo ring, wherein said ring formed by Rx and Ry is (c) R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic group, phenyl, or -CN; (d) R2 is hydrogen or a substituted or unsubstituted group selected from aryl or a C1-6 aliphatic group; and (e) each R5 is independently selected from -halo, -CN, -N02, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, or -N(R4)SO2R. Even more preferred compounds of formula X have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring; (b)-Rx is hydrogen or methyl and Ry is methyl, methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or an optionally substituted group selected from 2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted benzo ring or a 6-membered carbocyclo ring; (c) R1 is -halo, a C1-4 aliphatic group optionally substituted with halogen, or -CN; (d) R2 is hydrogen or a C1-6 aliphatic group; and (c) (e) each R5 is independently selected from -Cl, -F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -O(C1-4 aliphatic), C1-4 aliphatic, and -C02 (C1-4 aliphatic) . Another embodiment of this invention relates to compounds of formula XI: or a pharmaceutically acceptable derivative or prodrug thereof, wherein:. Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -R5, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; Rx and Ry are taken together with their intervening atoms to form a fused benzo ring or 5-8 membered carbocyclo ring, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3 ; T is a valence bond or a C1-4 alkylidene chain; R2 is -R or -T-W-R6; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, each R6 is independently selected from hydrogen or an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; and each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring. Compounds of formula XI are structurally similar to compounds of formula III except for the replacement of the pyrazole ring moiety by the triazole ring moiety. Preferred R2, Rx, Ry, and Ring D groups of formula XI are as described above for the formula III compounds. Preferred formula XI compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4-tetrahydroisoguinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; (b) Rx and Ry are taken together with their intervening atoms to form an optionally substituted benzo ring or 5-7 membered carbocyclo ring; and (a) (c) R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1-6 aliphatic group. More preferred compounds of formula XI have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro- 1H-isoindolyl, 2,3 -dihydro-lH-indolyl, isoquinolinyl, guinolinyl, or naphthyl; (b) R* and Ry are taken together with their intervening atoms to form a benzo ring or 5-7 membered carbocyclo ring, wherein said ring formed by Rx and RY is optionally substituted with -R, oxo, halo, -OR, -C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N{R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2, -N(R4)S0aN(R4)2, -N(R4)SO2R, or -OC (=0)N (R4) 2; (c) R2 is hydrogen or a substituted or unsubstituted group selected from aryl or a C1-6 aliphatic group; and (d) each R5 is independently selected from halo, oxo, CN, NO2, -N(R4)2, -CO2R, -CONH(R4) , -N(R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. Even more preferred compounds of formula XI have one or more, and more preferably all, of the features selected from the group consisting of: (a) Rx and Ry axe taken together with their intervening atoms to form a benzo ring or 6-membered carbocyclo ring, wherein said ring formed by Rx and Ry is optionally substituted with halo, CN, oxo, C1-6 alkyl, C1-6 alkoxy, (C1-6 alkyl) carbonyl, (C1-6 alkyl)sulfonyl, mono- or dialkylamino, mono- or dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy, or 5-6 membered heteroaryl; (b) each R5 is independently selected from -halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic; and (c) R2 is hydrogen or a C1-6 aliphatic group. Another embodiment of this invention relates to compounds of formula XII: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -Rs, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 1-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring is optionally and independently substituted by T-R3, and any substitutable nitrogen on said ring is substituted by R4; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R* on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, each R6 is independently selected from hydrogen or an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; and each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl ring or heteroaryl. Compounds of formula XII are structurally similar to compounds of formula IV except for the replacement of the pyrazole ring moiety by the triazole ring moiety. Preferred R2, Rx, Ry, and Ring D groups of formula XII are as described above for the formula TV compounds. Preferred formula XII compounds have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3- dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; (b) Rx is hydrogen or C1-4 aliphatic and Ry is T- R3, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted 5-7 membered unsaturated or partially unsaturated ring having 1-2 ring heteroatoms; and (c) R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1-6 aliphatic group. More preferred compounds of formula XII have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2, 3-dihydro-lff-indolyl, isoquinblinyl, quinolinyl, or naphthyl; (b) R* is hydrogen or methyl and Ry is -R, N(R)2, or -OR, or Rx and Ry are taken together with their intervening atoms to form a 5-7 membered unsaturated or partially unsaturated ring having 1-2 ring nitrogens, wherein said ring is optionally substituted with -R, halo, oxo, -OR, -C(=O)R, -COaR, -COCOR, -NO2/ -CN, -S(O)R, -S02R, -SR, -N(R)2, -CON(R4)2, -SO2N(R4)2, -OC(=0)R, (a) -N(R4)COR, -N(R4)CO2 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC (=0)N(R4) 2; (c) R2 is hydrogen or a substituted or unsubstituted gxoup selected from aryl or a C1-6 aliphatic group; and (d) each R5 is independently selected from halo, oxo, CN, NO2, -N(R4)2, -CO2R, -CONH(R4) , -N(R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or a substituted or unsubstituted group selected from 5-6 metnbered heterocyclyl, C6-10 aryl, or C1-6 aliphatic. Even more preferred compounds of formula XII have one or more, and more preferably all, of the features selected from the group consisting of: (a) Rx and Ry are taken together with their intervening atoms to form a 6-membered unsaturated or partially unsaturated ring having 1-2 ring nitrogens, optionally substituted with halo, CN, oxo, C1-6 alkyl, C1-6 alkoxy, (C1-6 alkyl) carbonyl, (C1-6 alkyl) sulfonyl, mono- or dialkylamino, mono- or dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy,; or 5-6 membered heteroaryl; (b) each R5 is independently selected from -halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted group selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic; and (c) R2 is hydrogen or a C1-6 aliphatic group. Another embodiment of this invention relates to compounds of formula XIII: or a pharmaceutically acceptable derivative or prodrug thereof, wherein: Z1 is nitrogen, CRa, or CH, and Z2 is nitrogen or CH; provided that one of Z1 and Z2 is nitrogen; G is Ring C or Ring D; Ring C is selected from' a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 metobered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl, said heteroaryl or heterocyclyl ring having 1-4 ring heteroatoms selected from nitrogen, oxygen or sulfur, wherein Ring D is substituted at any substitutable ring carbon by oxo or -Rs, and at any substitutable ring nitrogen by -R4, provided that when Ring D is a six-membered aryl or. heteroaryl ring, -R5 is hydrogen at each ortho carbon position of Ring D; R1 is selected from -halo, -CN, -N02, T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R8, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or Rl and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3, and any substitutable nitrogen on said ring formed by Rx and Ry is substituted by R4; T is a valence bond or a C1-4 alkylidene chain; R2 is -R or -T-W-R6; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -NO2, -CN, -S(O)R, -S(O)2R, -SR, -N(R)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7) C02( optionally substituted Cj.-6 aliphatic), -N(R)N(R)2, -C=NN(R4)2, -C=N-OR, -N (R7) CON (R7)2, -N(R7)SO2N(R7)2, -N{R4)SO2R, or -OC(=O)N(R7)2; each R is independently selected from hydrogen or an optionally substituted group selected from Ci-e aliphatic, C6_io aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R6 is independently selected from hydrogen, an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; each R8 is independently selected from an optionally substituted C1-4 aliphatic group, -OR6, -SR6, -COR6,- -SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or -CO2R6; and Ra is selected from halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02/ -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) C02 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N{R4) SO2N(R4) 2, -N(R4)SO2R, -OC(=O)N(R4)2, or an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms. Compounds of formula XIII may be represented by specifying Z1 and Z2 as shown below: Compounds of formula XIII are structurally similar to compounds of formula V except for the replacement of the pyrazole ring moiety by the triazole ring moiety. Preferred R2, Rx, Ry, Ra, and Ring G groups of formula XIII are as described above for the formula V compounds. Preferred formula XIII compounds have one or more, and more preferably all, of the .features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring, and R1 is -halo, an optionally substituted C1-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; or Ring D is an optionally substituted ring selected from a phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3 -dihydro- 1H-isoindolyl, 2,3 -dihydro- 1H-indolyl, isoquinolinyl, quinolinyl, or naphthyl ring; (b) Rx is hydrogen or C1-4 aliphatic and Ry is T- R3, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted 5-7 membered unsaturated. or partially unsaturated ring having 0-2 ring nitrogens; and (c) R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1-6 aliphatic group. More preferred compounds of formula XIII have one or more, and more preferably all, of the features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic group, phenyl, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 2,3-dihydro-1H-isoindolyl, 2,3- dihydro-lff-indolyl, isoquinolinyl, quinolinyl, or naphthyl; (b) Rx is hydrogen or methyl and Ry is -R, N(R4)2, or -OR, or Rx and Ry are taken together with their intervening atoms to form a benzo ring or a 5-7 membered carbocyclo ring, wherein said ring formed by Rx and Ry is optionally substituted with -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)a, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) C02 (optionally substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2/ -N(R4) SO2N(R4) 2, -N(R4)SO2R, or -OC(=O)N(R4)2; (c) R2 is hydrogen or a substituted or unsubstituted group selected from aryl, or a C1-6 aliphatic group; and (d) each Rs is independently selected from -halo, -CN, -N02, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4) , -N(R4)COR, -SO2N(R4)2, or -N(R4)SO2R, and, when Ring G is Ring D, Ring D is substituted by oxo or R5. Even more preferred compounds of formula XIII have one or more, and more preferably all, of the features selected from the group consisting of: (a) R is hydrogen or methyl and Ry is methyl, methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or an optionally substituted group selected from 2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry are taken together with their intervening atoms to form a benzo ring or a 6-membered carbocyclo ring wherein said ring formed by Rx and Ry is optionally substituted with halo, CN, oxo, C1-6 alkyl, C1-6 alkoxy, (C1-6 alkyl) carbonyl, (C1-6 alkyl) sulfonyl, mono- or dialkylamino, mono- or dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy, or 5-6 membered heteroaryl; (b) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R1 is -halo, a C1-4 aliphatic group optionally substituted with halogen, or -CN; or Ring D is an optionally substituted ring selected from phenyl, pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, isoquinolinyl, quinolinyl, or naphthyl; (c) R2 is hydrogen or a C1-6 aliphatic group; and (d) each R5 is independently selected from -Cl, -F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2/ -0(C1-4 aliphatic), C1-4 aliphatic, and -CO2(C1-4 aliphatic) , and when Ring G is Ring D, Ring D is substituted by oxo or R5. Representative compounds of formula IX are shown below in Table 8. In another embodiment, this invention provides a composition comprising a compound of formula IX and a pharmaceutically acceptable carrier. One aspect of this invention relates to a method of inhibiting GSK-3 activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula IX. Another aspect relates to a method of treating a disease that is alleviated by treatment with a GSK-3 inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula IX. Another aspect relates to a method- of enhancing glycogen synthesis and/or lowering blood levels of glucose in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula IX. This method is especially useful for diabetic patients. Another aspect relates to a method of inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition comprising a compound of formula IX. This method is especially useful in halting or slowing the progression of Alzheimer's disease. Another aspect relates to a method of inhibiting the phosphorylation of P-catenin in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a composition • comprising a compound of formula IX. This method is especially useful for treating schizophrenia. One aspect of this invention relates to a method of inhibiting Aurora activity in a patient, comprising administering to the patient a therapeutically effective amount of a composition comprising a compound of formula IX. ' . Another aspect relates to a method of treating a disease that is alleviated by treatment with an Aurora inhibitor, said method comprising the step of administering to a patient in need of such a treatment a therapeutically effective amount of a composition comprising a compound of formula IX. This method is especially, useful for treating cancer, such as colon, ovarian, and breast cancer. Another method relates to inhibiting GSK-3 or Aurora activity in a biological sample, which method comprises contacting the biological sample with the GSK-3 or Aurora inhibitor of formula IX, or a pharmaceutical composition thereof, in an amount effective to inhibit GSK-3 or Aurora. Each of the aforementioned compositions and methods directed to the inhibition of GSK-3 or Aurora, or the treatment of a disease alleviated thereby, is preferably carried out with a preferred compound of formula IX, as described above. The compounds of this invention may be prepared as illustrated by the Synthetic Methods below, by the Synthetic Examples described herein and by general methods known to those skilled in the art. General Synthetic Methods The general synthetic methods below provide a series of general reaction routes that were used to prepare compounds of this invention. Methods A-F below are particularly useful for preparing formula II compounds. In most cases. Ring C is drawn as a phenyl ring bearing an ortho R1 substituent. However, it will be apparent to one skilled in the art that compounds having other Ring C groups may be obtained in a similar manner. Methods analogous to methods A-F are also useful for preparing other compounds of this invention. Methods F-I below are particulary useful for preparing compounds of formula III or IV. Method A is a general route for the preparation of compounds wherein ring C is an aryl or heteroaryl ring. Preparation of the starting dichloropyrimidine 1 may be achieved in a manner similar to that described in Chem. Pharm. Bull., 30, 9, 1982, 3121-3124. The chlorine in position 4 of intermediate 1 may be replaced by an aminopyrazole or aminoindazole to provide intermediate 2 in a manner similar to that described in J. Med. Chem., 38, 3547-3557 (1995). Ring C is then introduced using a boronic ester under palladium catalysis (see Tetrahedron, 48, 37, 1992, 8II7-8126). This method is illustrated by the following procedure. A suspension of lff-quinazoline-2,4-dione (10.0 g, 61.7 mmol) in POCl3 (60 mL, 644 mmol) and N,N- dimethylaniline (8mL, 63.1 mmol) is heated under reflux for 2 h. Excess POCl3 is evaporated under vacuum, the residue is poured into ice, and the precipitate is collected by filtration. The crude solid 2,4- dichloroquinazoline product may be used without further purification. To a solution of 2,4-dichloro-quinazoline (3.3 g, 16.6 mmol) in anhydrous ethanol (150 mL) is added 5- methyl-lH-pyxazol-3-yl amine (3.2 g, 32.9 mmol). The mixture is stirred at room temperature for 4 h, and the resulting precipitate is collected by filtration, washed with ethanol, and dried under vacuum to afford (2-chloro- quinazolin-4-yl)-(5-methyl-lH-pyrazol-3-yl)-amine. To a solution of (2-chloro-guinazolin-4-yl) - (5- methyl-lH-pyrazol-3-yl)-amine (50 mg, 0.19 mmol) in DMF (1.0 mL) is added the desired arylboronic acid (0.38 mmol), 2M Na2C03 (0.96 mmol), and tri-t-butylphosphine (0.19 mmol). Under-nitrogen, PdCl2(dppf) (0.0II mmol) is added in one portion. The reaction mixture is then heated at 80°C for 5 to 10 hours, cooled to room temperature, and poured into water (2 mL). The resulting precipitate is collected by filtration, washed with water, and purified by HPLC. Methods B through F describe routes where the pyrazole ring system is introduced after Ring C and the . pyrimidine ring portion are first constructed. A versatile intermediate is the 4-chloropyrimidine 4, which is readily obtained from pyrimidinone 3 as shown in Method B(i). This reaction sequence is generally applicable for a variety of Ring C groups including aliphatic, aryl, heteroaryl, or heterocyclyl. See J. Med. Chem., 38, 3547-3557 (1995). For quinazoline ring systems (where Rx and Ry are taken together to form a benzo ring) , the useful intermediate 6 may be obtained by condensing an anthranilic acid or its derivative with a benzamidine as shown in Method B(ii) or by condensing a benzoylchloride with an anthranilamide as shown in Method B(iii) . Many substituted anthranilic acid, anthranilamide, benzamidine and benzoylchloride starting materials may be obtained by known methods. See Aust. J. Chem., 38, 467-474 and J. Med. Chem., 38, 3547-3557 (1995). Method B(iii) is illustrated by the following procedure. To a solution of anthranilamide (33 mmol) in THF and CH2Cl2 (1:1, 70 mL) is added the desired benzoylchloride (33 mmol) , and triethylamine (99 mmol) at room temperature. The mixture is stirred for about 14 hours. The resulting precipitate is collected by filtration, washed with CH2cl2 and water, and dried under vacuum. The crude 2-behzoylaminobenzamide may be used directly for the next step without further purification. To a solution of the above crude product (13 mmol) in ethanol (50 mL) is added NaOEt (26 mmol) at room temperature. The mixture is heated under reflux for 48 to 96 h. The solvent is evaporated and the "residue is neutralized using concentrated HC1 to pH 7. The product is then collected by filtration and dried under vacuum to provide 2-phenyl-3H-guinazolin-4-one that may be used without further purification. To a suspension of the above product (12 mmol) in POC13 (120 mmol) is added tri-n-propylamine (24 mmol) . The mixture is heated under reflux for lh. After removal of the excess POC13. by evaporation, the residue is dissolved in ethyl acetate, and washed with IN NaOH (twice) and water (twice). The organic layer is dried over MgS04, the solvent is evaporated under vacuum, and the crude product is purified by flash chromatography (eluting with 10% of ethyl actetate in hexanes) to give 4-chloro-2-aryl guinazoline. To a solution of 4-chloro-2-aryl guinazoline (0.16 mmol) in DMF (or THF, ethanol) (1 mL) is added the desired aminopyrazole or aminoindazole (0.32 mmol). The mixture is heated in DMF (or THF under reflux) at 100 to II0°C for 16 h (or in ethanol at 130-160°C for 16 hours) and then poured into water (2 mL) . The precipitate is collected by filtration and purified by HPLC. Methods C and D(i) above employ p-ketoesters 8 and 10, respectively, as pyrimidinone precursors. The substitution pattern of the Rx and Ry groups on the pyrimidinone ring will be reversed if a chlorocrotonate II (Synth. Comm, (1986), 997-1002), instead of the corresponding P-ketoester 10, is condensed with the desired benzamidine. These methods are illustrated by the following general procedure. To a solution of a p-ketoester (5.2' mmol) and amidinium chloride (5.7 mtriol) in ethanol (5 mL) .is added sodium ethoxide (7.8 mmol). The mixture is heated under reflux for 7-14 hours. After evaporation the resulting residue is dissolved in water, acidified with concentrated HC1 to pH 6, and then filtered to obtain a solid product 2-aryl-3H-pyrimidin-4-one (yield 75-87%) , which may be purified by flash column chromatography if needed. To this pyrimidinone (3.7 mmol) is added POC13 (4 tnL) and n-Pr3N (1.4 mL) . The mixture is heated under reflux for 1 hour. After evaporation of the excess POC13, the residue is dissolved in ethyl acetate, washed with IN NaOH solution (three times) and NaHCO3 (once) , and dried over MgS04. The solvent is removed under vacuum and the residue is purified by flash column chromatography eluting with 10% of ethyl acetate in hexanes to give 2- aryl-4-chloro-pyrimidine as a pale yellow syrup. This crude product may be treated with a 3-aminopyrazole or 3- aminoindazole as described above. Method D(ii) above shows a general route for the preparation of the present compounds, such as compound 40, wherein Ry is N(R4)2. See II Farmaco, 52(1) 61-65 (1997) . Displacement of the S-chloro group is exemplified here using morpholine. This method is illustrated by the following procedure. To a solution of 2-methylmalonic acid diethyl ester (5 mmol) and sodium ethoxide (15 mmol) is added the appropriate amidine salt (5 mmol) in ethanol (10 mL) and the reaction heated at reflux for 2-24 hours. The residue is dissolved in water and acidified with 2N HC1. The resulting precipitate is filtered off and further purified by flash chromatography (yield 5-35%) to afford the pyrimidinedione 37. To 37 (1.6 mmol) is added POC13 (32 mmol) and tri-n-propylamine (6.4 mmol) and the reaction refluxed is for lh. After evaporation of excess POC13, the residue is dissolved in ethyl acetate, basified with IN NaOH, separated and the aqueous phase twice more extracted with ethyl acetate. The combined organics are dried (sodium sulfate) and evaporated. Purification by flash chromatography provides the dichloropyrimidine (38) as a yellow oil in 23% yield. A solution of 38 (0.33 mmol) in methanol (5 mL) is treated with an amine, exemplified here using morpholine (0.64 mmol) and refluxed 1 hour. After evaporation of solvent, the residue is purified by flash chromatography to provide the mono-chloropyrimidine 39 as a colorless oil in 75% yield. The mono-chloropyrimidine, 39, (0.19 mmol) may be treated with a 3-aminopyrazole or 3-aminoindazole compound in a manner substantially similar those described above in Methods A and B. (J. Org. Chem (1993), 58, 414-418; J.Med.Chem., (1992), 35, 1515-1520; J.Org.Chem., 91967, 32, 313-214). This method is illustrated by the following general procedure. The enamine is prepared according to w. White, et al,J. Org Chem. (1967), 32, 213-214. The acyl isocyanate is prepared according to G Bradley, et al, J Med. Chem. (1992), 35, 1515-1520. The coupling reaction then follows the procedure of S Kawamura, et al, J. Org. Chem, (1993), 58, 414-418. To the enamine (10 mmol) in tetrahydrofuran (30 mL) at 0°C under nitrogen is added dropwise over 5 min a solution of acyl isocyanate (10 mmol) in tetrahydrofuran (5 tnL) . After stirring for 0.5 h> acetic acid (30 mL) is added, followed by ammonium acetate (50 mmol). The mixture is refluxed for 2 h with continuous removal of tetrahydrofuran. The reaction is cooled to room temperature and is poured into water (100 mL) . The precipitate is filtered, washed with water and ether and dried to provide the 2-aryl-3H-pyrimidin-4-one. Method F shows a general route for the preparation of the present compounds wherein Rx and Ry are . taken together to form a 5-8 membered partially unsaturated saturated or unsaturated ring having 1-3 heteroatoms. The condensation of a 2-amino-carboxylic acid, such as 2-amino-nicotinic acid 13, and an acid chloride 7 provides an oxazinone 14. Treatment of 14 . with ammonium hydroxide will furnish the benzamide 15 . which may be cyclized to a 2- (substituted) -pyrido [2,3- d] [l,3]pyrimidin-4-one 16. This method is illustrated by the following procedure. 2-(Trifluoromethyl)benzoyl chloride (4.2 ml, 29.2 mmol) is added dropwise to a solution of 2- aminonicotinic acid (2.04g, 14.76 mmol) in 20 ml of pyridine. The reaction mixture is. heated at 158 C for 30 min then cooled to room temperature. The reaction is poured into 200 ml of water and an oil forms which solidifies upon stirring. The solid is collected by vacuum filtration and washed with water and diethyl ether. The product is dried to give 2- (2- trifluoromethyl-phenyl)-pyrido[2, 3-d] [1,3]oxazin-4-one (2.56 g, 60% yield) which may be used in the next step without further purification. 2- (2-Trif luoromethyl-phenyl) -pyrido [2,3- d] [1,3] oxazin-4-one (2.51g) is stirred in 30% ammonium hydroxide (25 ml) at room temperature overnight. The resulting precipitate is filtered and rinsed with water and diethyl ether. The precipitate is dried under vacuum at 50 C overnight to give 2- (2-trifluoromethyl- benzoylamino) -nicotinamide (850 mg, 33% yield) 2- (2-Trifluoromethyl-benzoylamino) -nicotinamide (800mg, 2.6mmol) is dissolved in 10ml of ethanol. Potassium ethoxide (435mg, 5.2mmol) is added to the solution which is heated to reflux for 16 h. The reaction mixture is evaporated in vacuo to afford a gummy residue that is dissolved in water and acidified with 10% sodium hydrogen sulfate to pH 7. The resulting precipitate is filtered and dried under vacuum at 50 C to give 2 - (2 -trifluoromethyl-phenyl) -3H-pyrido [2,3- d] pyrimidin- 4 - one. Method G Method G is analogous to Method B(i) above. This method is illustrated by the following general procedure. 2- (3,4-Dichloro-phenyl) -3H-quinazolin-4-one (lg, 3.43 mmol) is suspended in phosphorus oxychloride (4 mL) and the reaction mixture was stirred at II0°C for 3 hours. The solvents are then evaporated and the residue is treated carefully with an ice cold aqueous saturated solution of NaHCO3. The solid is collected by filtration and washed with ether to give 4-chloro-2- (3,5-dichloro- phenyl)-quinazoline as a white solid (993 mg, 93%). To 4-chloro-2- (3,5-dichloro-phenyl) -quinazoline (4.00mg, 1.29 mmol) in THF (30 mL) is added 3-amino-5- methyl pyrazole (396 mg, 2.S8 mmol) and the reaction mixture is heated at 65°C overnight. The solvents are then evaporated and the residue triturated with ethyl acetate, filtered and washed with a minimum amount of ethanol to give [2- (3,4-dichlorophenyl) -quinazolin-4-yl] - (5-methyl-2J?-pyrazol-3-yi)-amine as a white solid (3II mg 65%): mp 274°C; XH NMR (DMSO) 8 2.34 (3H, s) , 6.69 (1H, s), 7.60 (1H, m), 7.84 (1H, d), 7.96 (2H, d), 8.39. (1H, dd) , 8.60 (1H, d), 8.65 (1H, d), 10.51 (1H, s) , 12.30 (1H, S) ; IR (solid) 1619, 1600, 1559, 1528, 1476, 1449, 1376, 1352, 797, 764, 738; MS 370.5 (M+H)+. The THF solvent used, in'the previous step may be replaced by other organic solvents such as ethanol, N,N-dimethylformamide, or dioxane. Method H Method H shows routes in which a Ring D aryl group bearing a halogen (X is Br or I) may be converted to other formula III compounds. Method H(i) shows a phenylboronic acid coupling to Ring D to provide compound 18 and Method H(ii) shows an acetylene coupling to provide compound 19. Substituent X in compound 17 may be bromine or iodine. These methods are illustrated by the following procedures. Method H(i). To a mixture of [2-(4-bromo- phenyl) -quinazolin-4-ylJ - (5-methyl-2H-pyrazol-3-yl) -amine (196 mg, 0.51 mmol) and phenylboronic acid (75 mg, 0.62 mmol) in THF/water (l/l, 4 mL) is added Na2CO3 (219 mg, 2.06 mmol), triphenylphosphine (9mg, 1/15 mol%) and palladium acetate (1 mg, 1/135 mol%). The mixture is heated at 8 0°C overnight, the solvents are evaporated and the residue is purified by flash chromatography (gradient of CH2Clz/MeOH) to give (2-biphenyl-4-yl-quinazolin-4-yl) - (5-methyI-21T-pyrazol-3-yl) -amine as a yellow solid (99 mg, SUli'-HHMR (DMSO) 8 2.37 (3H, s) , 6.82 (1H, s) , 7.39- 7.57 (4H, m), 7.73-7.87 (6H, m) , 8.57 (2H, d) , 8.67 (1H, d), 10.42 {1H, s), 12.27 (1H, s); MS 378.2 (M+H)+ Method H(ii). To a mixture of [2-(4-bromo- phenyl) -guinazolin-4-yl] - (5-methyl-2J-T-pyrazol-3-yl) -amine (II4 mg, 0.3 imnol) , and trimethylsilylacetylene (147 mg, 1.5 mmoDin DMF (2 mL) is added Cul (1.1 mg, 1/50 mol%) , Pd(PPh3)2Cl2 (4.2 mg, 1/50 mol%) and triethylamine (121 mg, 0.36 mrnol) . The mixture is heated at 120°C overnight and the solvent is evaporated. The residue is triturated in ethyl acetate and the precipitate is collected by filtration. ? To the above precipitate suspended in THF (3 mL). is added tetrabutylammonium fluoride (1M in THF, 1.leq). The reaction mixture is stirred at room temperature for two hours and the solvent is evaporated. The- residue is purified by flash chromatography (gradient of CH2Cl2/Me0H) to give [2- (4-ethynylphenyl) -quinazolin-4- yl] - (5-tnethyl-2i?-pyrazol-3-yl)-amine as a white solid (68 mg, 70%): XH NMR (DMSO) 5 2.34 (3H, s)', 4.36 (1H, s) , 6.74 (1H, s), 7.55 (1H, m), 7.65 (2H, d) , 7.84 (2H, m), 8.47 (2H, d), 8.65 (1H, d), 10.43 (1H, s), 12.24 (1H, s); MS 326.1 (M+H)+ Method I above shows a general route for the preparation of the present compounds wherein ring D is a heteroaryl or heterocyclyl ring directly attached to the pyrimidine 2-position via a nitrogen atom. Displacement of the 2-chloro group, exemplified here using piperidine, may be carried out in a manner similar to that described in J. Med. Chem., 38, 2763-2773 (1995) and J. Chem. Soc., 176-6-1771 (1948) . This method is illustrated by the following procedure. To a solution of (2-chloro-quinazolin-4-yl) - (lfl"-indazol-3-yl)-amine (1 equivalent, 0.1-0.2 mmol) in N, N-dimethylacetamide (1 ml) is added the desired amine (3 equivalents) . ,The resulting mixture is maintained at 100°C for 6 h and then purified by reverse-phase HPLC. Method J above shows the preparation of compounds of formula V via the displacement of a chloro group from an appropriately substituted pyridyl ring. Method J(i) is a route for preparing compounds of formula Va (see Indian J. Chem. Sect.B, 35, 8., 1996, 871-873) . Method J(ii) is a route for preparing compounds of formula Vb (see Bioorg. Med. Chem.,6, 12, 1998, 2449- 2458) . For convenience, the chloropyridines 21 and 23 are shown with a phenyl substituent corresponding to Ring D of formula V. It would be apparent to one skilled in the art that Method J is also useful for preparing compounds of formula V wherein Ring D is heteroaryl, heterocyclyl, carbocyclyl or other aryl rings. Method J is illustrated by the following procedures. Method J(i). (5-Methyl-2ff-pyrazol-3-yl) - (2- phenyl-quinolin-4-yl) -amine. To 4-chloro-2- phenylquinoline (J. Het. Chem., 20, 1983, 121-128)(0.53g, 2.21 mmol) in diphenylether (5 mL) was added 3-amino-5- methylpyrazole (0.43g, 4.42 mmol) and the mixture was heated at 200°C overnight with stirring. To the cooled mixture was added petroleum ether (20 mL) and the resulting crude precipitate was filtered and further washed with petroleum ether. The crude solid was purified by flash chromatography (SiO2, gradient DCM-MeOH) to give the title compound as a white solid: mp 242-244°C; 1H NMR phenyl - isoguinol in-1 -y 1) - amine. To 1 - chloro - 3 - phenylisoquinoline (J. Het. Chem., 20, 1983, 121- 128)(0.33g, 1.37 mmol) in dry DMF (5 mL) was added 3- amino-5-methylpyrazole (0.27g, 2.74 mmol) and potassium carbonate (o.57g, 4.13 mmol)and the mixture was heated under reflux for 6 hours. The mixture was cooled and the bulk of DMF was evaporated. The residue was extracted twice with ethyl acetate and the combined organic layers were washed with brine, dried (MgSO4) , filtered and concentrated. The crude was purified by flash - . chromatography (SiO2, gradient DCM-MeOH) to give the title compound as a colourless oil; 1H NMR (MeOD) ? 2.23 (3H, s), 5.61 (1H, s), 7.41 (1H, m) , 7.52 (2H, m) , 7.62 (1H, tn) , 7.81(1H, m), 8.07(lH, d) , 8.19(2H, m), 8.29(1H, s), 8.54 (1H, d); MS 301.2 (M+H)+ Method K shows a route for the preparation of compounds of formula VI. A versatile starting material is 2,4,6-trichloro-[1,3,5]triazine 25 in which the chlorine substituents may be sequentially displaced. The displacement of one of the chlorines by an aryl Grignard reagent or an aryl boronic acid is described in PCT patent application WO 01/25220 and Helv. Chim. Acta, 33, 1365 (1950). The displacement of one of the chlorines by a heteroaryl' ring is described in WO 01/25220; J. Het. Chem., II, 417 (1974); and Tetrahedron 31, 1879' (1975). These reactions provide a 2,4-dichloro-(6- substituted)[1,3,5]triazine 26 that is a useful intermediate for the preparation of compounds of formula VT. Alternatively, intermediate 26 may be obtained by constructing the triazine ring by known methods. See US patent 2,832,779; and US patent 2,691020 together with J. Am. Chem. Soc. 60, 1656 (1938). In turn, one of the chlorines of 26 may be displaced as described above to provide 2-chloro-(4, 6-disubstituted) [1,3,5]triazine 27. Method L shows a route for preparing compounds of formula VTI. For illustration purposes the trifluoromethylchalcone 28 is used as a starting material; however, it would be apparent to one skilled in the art that other rings may be used in place of the trifluoromethylphenyl and phenyl rings of compound 28. Substituted chalcones may be prepared by known methods, for example as described in the Indian J. Chemistry, 32B, 449 (1993). Condensation of a chalcone with urea provides the pyrimidinone 29, which may be treated with POC13 to give the chloropyrimidine 30. See J. chem. Eng. Data, 30(4) 512 (1985) and Egypt. J. Chem., 37(3), 283 (1994) . In an alternative approach to compound 30, one of the aryl rings attached to the pyrimidine is introduced by displacement of of the. 4-chloro group of 2,4-dichloro- (6-aryl) -pyrimidine by an aryl boronic acid using a palladium catalyst such as (Ph3P)4Pd in the presence of a base such as sodium carbonate as described in Bioorg. Med. Lett., 9(7), 1057 (1999).- Displacement of the chlorine of compound 30 by an appropriate aminopyrazole provides compounds of this invention, such as 31. The last step of this method is illustrated by the following procedure. [4- (4-Methylpiperidin-l-yl) -pyrimidin-2-yl] - (5- methyl-2H-pyrazol-3-yl)-amine. To a solution of 2- chloro-4 - (4-methylpiperidin-1 -yl) -pyrimidine (prepared using a procedure similar to the one reported in Eur. J. Med. Chem., 26(7) 729(1991)) (222 mg, 1.05 mmol) in BuOH (5 mL) was added 3-amino-5-methyl-2H-pyrazole (305mg, 3.15 mmol) and the reaction mixture was then heated under reflux overnight. The solvent was evaporated and the residue dissolved in a mixture ethanol/water (1/3, 4 mL) . Potassium carbonate (57mg, 0.41 mmol) was added and-the mixture was stirred at room temperature for 2 hours. The resulting suspension was filtered, washed with water twice and rinsed with ether twice to give the title . compound as a white solid (143mg, 50%): mp 193-195°C; XH NMR (DMSO) 8 0.91 (3H, d) , 1.04 (2H, m) , 1.67 (3H, m) , 2.16 (3H, s), 2.83 (2H, t), 4.31 (2H, m) , 6.19 (2H, m) , 7.87 (1H, d), 8.80 (1H, br s), II.71 (1H, s); IR (solid) 1627, 1579, 1541, 1498, 1417, 1388, 1322-, 1246; MS 273.3(M+H)+. Method M Method M provides routes for obtaining compounds of formula VTII. A general procedure far displacing the chlorine of a 4-chloro-6-substituted- pyridazine, 32, with an appropriately substituted pyrazole to provide VTIIa is described in J. Het. Chem., 20, 1473 (1983) . Analogous reactions may be carried out as follows: (a) with 3-chloro-5-substituted-pyridazine, 33, to provide VTIIb is described in J. Wed. Chem., 41(3), 3II (1998); (b) with 5-chloro-3-substituted- [1,2,4] triazine, 34, to provide VTIIc is described in Heterocydes, 26(12), 3259 (1987); and (c) with 3-chloro- 5-substituted- [1,2,4] triazine, 35, to provide VXIXd is described in Pol. J. Chem., 57, 7, (1983); Xndian J". Chem. Sect. B, 26, 496 (1987); and Agric. Biol. Chen?., 54(12), 3367 (1990). An alternative procedure to compounds of formula VTXlc is described in Indian J. Chew. Sect. B, 29(5), 435 (1990). Compounds of formula IX are prepared by methods substantially similar to those described above for the pyrazole-containing compounds of formula I. Methods A-J may be used to prepare the triazole-containing compounds' of formula IX by replacing the amino-pyrazole compound with an amino-triazole compound. Such methods are specifically exemplified by Synthetic Examples 415-422 set forth below. The amino-triazole intermediate may be obtained by methods described in J. Org. Chem. USSR, 27, 952-957 (1991). Certain synthetic intermediates that are useful for preparing the protein kinase inhibitors of this invention are. new. Accordingly, another aspect of this invention relates to a 3-aminoindazole compound of formula A: where R10 is one to three substituents that are each independently selected from fluoro, bromo, Ci-S haloalkyl, nitro, or 1-pyrrolyl. Examples of such compounds include the following: wherein Rx and Ry are as defined above; R1 is selected from Cl, F, CF3, CN, or NO2; and is one to three substituents that are each independently selected from H, Cl, F, CF3/ N02, or CN; provided that R1 and Rs are not simultaneously Cl. Examples of compounds of formula B are shown below: In order that the invention described herein may be more fully understood, the following examples • are set forth. It should be understood that these examples are for illustrative purposes only and are not to be construed as limiting this invention in any manner. SYNTHETIC EXAMPLE The following HPLC methods were used in the analysis of the compounds as specified in the Synthetic Examples set forth below. As used herein, the term "Rt" refers to the retention time observed for the compound using the HPLC method specified. HPLC-Method A: Column: C18, 3 um, 2.1 X 50 mm, "Lighting" by Jones Chromatography. Gradient: 100% water (containing 1% acetonitrile, 0.1% TFA) to 100% acetonitrile (containing 0.1% TFA) over.4.0 min, hold at 100% acetonitrile for 1.4 min and return to initial conditions. Total run time 7.0 min. Flow rate: 0.8 mL/min. HPLC-Method B: Column: C18, 5 um, 4.6 X 150 mm "Dynamax" by Rainin Gradient: 100% water (containing 1% acetonitrile, 0.1% TFA) to 100% acetonitrile (containing 0.1% TFA) over 2 0 min,hold at 100% acetonitrile for 7.0 min and return to initial conditions. Total run time 31.5 min. Flow rate: 1.0 mL/min. HPLC-Method C: Column: Cyano, 5 um, 4.6 X 150 mm "Microsorb" by Varian. Gradient: 99% water (0.1% TFA); 1% acetonitrile (containing 0.1% TFA) to 50% water (0.1% TFA),' 50% acetonitrile (containing 0.1% TFA) over 20 min, hold for 8.0 min and return to initial conditions. Total run time 30 min. Flow rate: 1.0 mL/min. HPLC-Method D: Column: Waters (YMC) ODS-AQ 2.0x50mm, S5, 120A. Gradient: 90% water (0.2% Formic acid), 10% acetonitrile (containing 0.1% Formic acid) to 10% water (0.1% formic acid), 90% acetonitrile (containing 0.1% formic acid) over 5.0 min, hold for 0.8 min and return to initial conditions. Total run time 7. 0 min. Flow rate: 1.0 mL/min. HPLC-Method E: Column: 50x2.0mm Hypersil C18 BDS;5 ?m Gradient: elution 100% water (0.1% TFA), to 5% water (0.1% TFA), 95% acetonitrile {containing 0.1% TFA) over 2.1 min, returning to initial conditions after 2.3 min. Flow rate; 1 mL/min. Example 1 [2-(2-Clorophenyl)-5,6-dimethylpyrimidin.-4-yl]- {5-Methyl-2H-pyrazol-3-yl)-amine (II-l) : ^-HNMR (500 MHz, DMSO-d6) 610.4 (s, br, 1H) , 7.74 (m, 2H) , 7.68 (m, 1H) , 7.60 (m, 1H), 6.39 (S, 1H), 2.52 (s, 3H), 2.30 (s, 3H), 2.22 (s, 3H);MS 314.1 (M+H). Example 2 [2- (2-Chloro-phenyl)-6,1,8, 9-tetrahydro-5H- cycloheptapyrimidin-4-yl3 - (lH-indazol-3-yl) -amine (II-2) : Prepared in 30% yield. 1HNMR (500MHz, DMSO-d6) 5 1.72 (m, 4H), 1.91 (m, 2H), 3.02 (m, 4H), 7.05 (t, 1H), 7.33 (t, 1H), 7.39 (m, 1H), 7.47 (d, 1H), 7.55 (m, 3H), 7.59 (d, 1H), 10.4.(m, 1H) , 13.II (br. S, 1H) ; EI-MS 390.2 (M+H); HPLC-Method A, Rt 2.99 min. Example 3 (5-Fluoro-lH-indazol-3-yl)- [2-(2- trifluoromethyl-phenyl) -5,6,7,8-tetrahydro-pyrido[3,4- d]pyrimidin-4-yl]-amine (II-3) : Compound II-18 (90 mg, 0.17 mmol) was treated with an equal weight of Pd/C (10%) in 4.4% formic acid in MeOH at room temperature for 14 h. The mixture was filtered through celite, the filtrate was evaporated, and crude product was purified by HPLC to provide 18 mg (24%) of the desired product as pale yellow Example 16 (5-Fluoro-lH-indazol-3-yl) - [2- (2- trifluoromethyl-phenyl) -5,6,7,8-tetrahydro-pyrido [4,3- dlpyrimidin-4-yl] -amine (II-16) -. A solution (of compound II-12 (45mg, 0.087 mmol) in methanol (4.4% HCOOH) was treated with an equal weight of Pd/C (10%) at room temperature for 14 h. The mixture was filtered through celite, the filtrate evaporated, and the crude product was purified by preparative HPLC to provide 15 mg (41%) of the desired product as yellow solid. 1HNMR (500 MHz, Prepared in 58% yield. 1HNMR (500 MHz, DMSO-d6) 813.0 (s, 1H), 10.3 (s, br, 1H), 7.74 (m, 4H), 7.51 (d, 1H) , 7.47 (d, 1H), 7.32 (t, 1H), 7.03 (t, 1H), 2.82 (m, 2H), 2.73 (lh, 2H), 1.90 (m, 4H) ppm; LC-MS (ES+) 410.21 (M+H); HPLC-Method A, Rt 2.99 min. Example 18 (7-Benzyl-2- (2 - trifluoromethyl-phenyl) - 5, 6,7, 8-tetrahydro-pyrido [4,3-d] pyrimidin-4-yl)-(5- fluoro-U?-indazol-3-yl)-amine (II-18): Prepared from compound Bll in 92% yield. 1HNMR (500 MHz, DMSO-d6) 812.9 {s, 1H) , 10.5 (s, br, 1H), 9.58 (s, 1H, TFA-OH), 7.71 (d, 1H), 7.52 (m, 9H), 7.19 (m, 2H), 4.57 (s, 2H) , 4.20 (m, 2H) , 3.70 (m, 2H) , 3.00 (m, 2H) ppm; LC-MS (ES+) 519.23 (M+H); HPLC-Method A, Rt 3.23 min. Example 19 (lff-Indazol-3-yl) - [6-methyl-2- (2- trifluoromethyl-phenyl) -pyrimidin-4-yl] -amine (II-19) : Prepared in 42% yield. Melting point 235-237°C; XHNMR (500 MHz, DMSO) 8 2.44 (3H, s) , 7.09 (1H, J=7.5 Hz, t) , 7.40 (1H, J=7.1 Hz, t), 7.49 (1H, J=8.3 Hz, d), 7.70 (3H, m) , 7.79 (1H, J=7.3 Hz, t) , 7.87 (1H, J=8.3 Hz, d) , 8.03 (1H, J=7.7 Hz, d) , 10.3 (1H, s), 12.6 (1H, s) ppm; HPLC- Method A, Rt 2.958 min; MS (P1A) 370.2 (M+H)+. Example 20 (lH-Indazol-3-yl) - [6-phenyl-2- (2- tr if luoromethyl-phenyl) -pyrimidin-4-yl] -amine (12-20) : Prepared in 32% yield. ^HNMR (500 MHz, DMSO) 8 6.94 (1H, J=7.4 Hz, t), 7.24 (1H, J=7.4 Hz, t) , 7.33 (1H, J=8.4 Hz, d), 7.42 (3H, m), 7.57 (1H, J=7.3 Hz, t) , 7.68 (2S, tn) , 7.75 (1H, J=7.9 Hz, d), 7.93 (3H, m), 8.18 (1H, br s), 10.45 (1H, br s) , 12.5 (1H, br s) ppm; HPLC-Method A, Rt 4.0 min; MS (FIA) 432.2 (M+H)+ . Example 21 (lff-Indazol-3-yl) - [6- (pyridia-4-yl) -2- (2- trifluoromethyl-phenyl)-pyrimidin-4-yl]-amine (II-21) : Prepared in 12% yield. 1HNMR (500 MHz, DMSO) 5 7.16 (1H, J=7.4 Hz, t), 7.46 (1H, J=7.6 Hz, t) , 7.55 (1H, J=8.3 Hz, d) , 7.80 (1H, J=7.2 Hz, t), 7.90 (2H, m), 7.97 (1H, J=7.8 Hz, d) , 8.09 (1H, br) , 8.22 (2H, J=4.9 Hz, d) , 8.45 (1H, br s), 8.93 (2H, J=4.8Hz, d) , 10.9 (1H, br s) , 12.8 (1H, br s) ppmj HPLC-Method A, Rt 3.307 min; MS (FIA) 433.2 (M+H)+ Example 22 (lff-Xndazol-3-yl) - [6- (pyridin-2-yl) -2- (2- trifluoromethyl-phenyl)-pyrimidin-4-yl]-amine (II-22): Prepared in 42% yield. 1HNMR (500 MHz, DMSO) 8 7.07 (1H, J=7.4 Hz, t), 7.36 (1H, J=7.4 Hz, t) , 7.46 (1H, J=7.4 Hz, . d) , 7.53 (1H, J=5.0 Hz, t), 7.70 (1H, J=7.4 Hz, t), 7.79 (1H, J=7.1 Hz, t) , 7.83 (1H, J=7.4 Hz, d) , 7.88 (1H, J=7.8 Hz, d), 7.97 (1H, J=7.7 Hz, t) , 8.02 (1H, J=5.5 Hz, br d) , 8.36 (1H, J=7.8Hz, d) , 8.75 (2H, J=4.1Hz, d) , 10.5 (1H, br s) , 12.7 (1H, br s) ppm; HPLC-Method A, Rt 3.677 min; MS (FIA) 433.2 (M+H) + . Example 23 [6- (2-Chlorophenyl) -2- (2-trifluoromethyl- phenyl) -pyrimidin-4-yl] - (lH-indazol-3-yl) -amine (II-23) : Prepared in 44% yield; XHNMR (500 MHz, DMSO) S 7.08 (1H, J=7.5 Hz, t) , 7.37 (1H, J=7.5 Hz, t) , 7.45 (1H, j=8.4 Hz, d), 7.51 (2H, m), 7.61 (1H, J=7.4, 1.9 Hz, dd), 7.69 (2H, m) , 7.79 (2H, J=4.0 Hz, d) , 7.86 (3H, J=7.8 Hz, d) , 8.04 (2H, J=6.2 Hz, br d) , 10.7 (1H, br s) , 12.6 (1H, br s) ppm; HPLC-Method A, Rt 3.552 min; MS (FIA). 466.2 (M+H) + . Example 24 [5,6 -Dimethyl - 2 - (2 - trif luoromethyl -phenyl) - pyrimidin-4-yl] - (lH-indazol-3-yl)-amine (II-24) : Prepared in 35% vield: mo 183-18C°C: XHNMR (500 MHz. DMSO) 5 2.14 (3H, s) , 2.27 (3H, s) , 6.85 (1H, J=7.5 Hz, t) , 7.15 (1H, J=7.6 Hz, t), 7.32 (3H, m), 7.38 (1H, J=7.5 Hz, t), 7.42 (1H, J=7.4 Hz, t) , 7.53 (1H, J=7.6Hz, d) , 8.88 (1H, s) , 12.5 (1H, s) ppm; HPLC-Method A, Rt 2.889 min. ; MS (FIA) 384.2 (M+H)'. Example 25 [5, 6-Dimethyl-2- (2-trifluoroxnethyl-plaenyl) - pyrimidin-4-ylJ - (5-fluoro-lff-indazol-3-yl) -amine (II-25) : Prepared in 44% yield. Melting point 160-163°C; ^-HNMR (500 MHz, DMSO) 5 2.27 (3H, s) , 2.40 (3H, s) , 7.16 (2H, m) , 7.44 (2H, m), .7.52 (1H, J=7.4 Hz, t), 7.57 (1H, J=7.4 Hz, t) , 7.67 (1H, J=7.8 Hz, d) , 9.03 (1H, s) , 12.75 (1H, s) ppm; HPLC-Method A, Rt 2.790 min,- MS (FIA) 402.2 (M+H)+. Example 26 [2- (2-Chlorophenyl) -5, 6-dimethyl-pyrimidin-4- yl]-(Iff-indazol-3-yl)-amine (II-26): Prepared in 30% yield. 1HNMR (500 MHz, DMSO) 8 2.14 (3H, s) , 2.33 (3H, s), 6.84 (1H, j=7.4 Hz, t), 7.13 (1H, J=7.4 Hz, t), 7.19 (1H, J=6.9 Hz, br t), 7.27 (1H, J=7.4 Hz, d) , 7.32 (3H, brm), 7.37 (1H, J=7.1 Hz, d) , 10.0 (1H, br), 12.8 (1H, br s) ppm; 8 2.919 min; MS (FIA) 350.1 (M+H)+. Example 27 [5,6-Dimethyl-2- (2-trifluoromethyl-phenyl) - pyrimidin-4-yl] - (7-f luoro-lff-indazol-3-yl) -amine (II-27) :: Prepared in 92% yield. 1HNMR (500 MHz, DMSO) 8 2.33 (3H, s), 2.50 (3H, s)I 6.97 (1H, m), 7.15 (1H, m) , 7.30 (1H, J=8.1 Hz, d), 7.65 (3H, m), 7.76 (1H, J=7.5 Hz, d) , 10.0 (1H, s) , 13.4 (1H, s) ppm; HPLC-Method A, Rt 3.053 min; MS (FIA) 402.2 (M+H) + . Example 28 (5,7-Difluoro-lH-indazol-3-yl)-[5,6-Dimethyl- 2-(2-trifluoromethyl-phenyl) -pyrimidin-4-yl]-amine (II- 28).: Prepared in 50% yield. ^-HNMR (500 MHz, DMSO) 8 2.42 (3H, s) , 2.63 (3H, s) , 7.22 (1H, J=7.6 Hz, d) , 7.38 (1H, J=9.3, 1.7 Hz, dt), 7.71 (1H, m) , 7.75 (1H, J=7.0 Hz, d) , 7.79 (1H, J=6.7 Hz, d) , 7.86 (1H, J=8.0 Hz, d) , 10.0. (1H, s) , 13.2 (1H, s) ppm; HPLC-Method-A, Rt 3.III min; MS (FIA) 420.2 (M+H)+.. Example 29 [2- (2-Chlorophenyl) -5, 6-dimethyl-pyrimidin-4- yl]-(5,7-difluoro-lH-indazol-3-yl)-amine (II-29): Prepared in 58% yield. ^UNMR (500 MHz, DMSO) 8 2.47 (3H, s), 2.66 (3H, s), 7.44 (2H, m) , 7.53 (1H, m) , 7.64 (3H, m) , 10.4 (1H, br) , 13.8 (1H, br s) ppm; HPLC-Method A, Rt 2.921 min; MS (FIA) 386.1 (M+H)+. Example 3 0 [2- (2-Chlorophenyl) -5, 6-dimethyl-pyrimidin-4- yl] - (7-fluoro-lH-indazol-3-yl)-amine (II-30): Prepared in 70% yield. ^-HNMR (500 MHz, DMSO) 8 2.35 (3H", s) , 2.51 (3H, s) , 7.03 (1H, J=7.8, 4.4 Hz, dt) , 7-22 (1H, m) , 7.33 (1H, J=7.4 Hz, t) , 7.42 (1H, m) , 9.19 (1H, s) , 13.3 (1H, s) ppm; HPLC-Method A, Rt 2.859 min; MS. (FIA) 368.2 . (M+H) + . Example 31 [2- (2-Chlorophenyl) -5, 6-dimethyl-pyrimidin-4- yl] - (5-f luoro-lH-indazol-3-yl) -amine (II-31): Prepared in 86% yield. 1HNMR (500 MHz, DMSO) 8 2.49 (3H, s), 2.68 (3H, s) , 7.38 (1H, J=9.0 Hz, t) , 7.54 (2H, m) , 7.67 (4H, m) , 10.5 (1H, br), 13.2 (1H, br s) ppm; HPLC-Method A, Rt 2.850 min; MS (FIA) 368.1 (M+H) + . Example 32 [2-(2,4-Dichlorophenyl)-5, e-dimethyl- pyrimidin^-yl] - (lff-indazol-3-yl)-amine (II-32): Prepared in 52% yield. 1HNMR (500 MHz, DMSO) 5 2.46 (3H, s) , 2.64 (3H, s) , 7.16 (1H, J=7.5 Hz, t) , 7.46 (1H, J=7.6 Hz, t) , 7.61 (2H, m) , 7.68 (2H, J=8.2 Hz, d) , 7.82 (1H, m) , 10.2 (1H, br) , 13.0 (1H, br s) ppm; HPLC-Method A, Rt 2.983. min; MS (FIA) 384.1 (M+H). Example 33 (5-Methyl-2ff-pyrazol-3-yl) - [2- (2- methylpnenyl)-quinazolin-4-yl]-amine (II-33): 1HNMR (DMSO) 5 1.21 (3H,s), 2.25 (3H, s) , 6.53 (1H, s), 7.38 (4H, m) , 7.62 (1H, d) , 7.73 (1-H, d) , 7.81 (1H, d) , 7.89 (1H, t) , 8.70 (1H, s), 12.20 (1H, s) ; MS 316.3 (M+H)+. Example 34 [2- (2,4-Dif luorophenyl) -quinazolin-4-yl] - (5- methyl-2ff-pyrazol-3-yl)-amine (II-34): 1HNMR (500 MHz, DMSO-d6) 812.4 (br s, 1H) , 10.8 (br s, 1H) , 8.58 (d, 1H) , 7.97 {m, 1H) , 8.36 (m, 1H) , 7.85 (m, 1H) , 7.60 (m, 1H) , 6.62 (s, 1H) , 2.30 (s, 3H) ; MS 338.07 (M+H). Example 35 [2- (2,5-Dimethoxypb.enyl) -quinazolin-4-yl] - (5- methyl-2H-pyrazol-3-yl)-amine (II-35): 1HNMR (500 MHz, DMSO-d6) 812.5 (br s, 1H) , 8.68 (br, 1H) , 7.92 (t, J = 7.5 Hz, 1H), 7.86 (d, J = 8.2. Hz, 1H) , 7.65 (t, J = 7.5 Hz, 1H), 7.45 (s, 1H) , 7.14 (m, 2H), 6.51 (s, 1H), 3.79 (s, 3H), 3.67 (s, 3H), 2.14 (s, 3H); MS 362.2 (M+H). Example 36 [2- (2-Chlorophenyl) -quinazolin-4-yl] - (5- methyl-2H-pyrazol-3-yl)-amine (II-36): 1HNMR (500 MHz, DMSO-d6) 8II.8 (br, 1H) , 8.80 (d, J =8.3 Hz, 1H) , 8-00 (t, J = 7.6 Hz, 1H), 7.82 (d, J = 8.3 Hz, 1H) , 7.78 (m, 2H), 7.67 (d, J = 7.8 Hz, 1H) , 7.61 (t, J = 7.0 Hz, 1H) , 7.55 (t, J = 7.4 Hz, 1H) , 6.56 (s, 1H), 2.18 (s, 3H); MS 336.1 (M+H). Example 37 [2- (2-Metnoxyphenyl) -quinazolin-4-yl] - (5- methyl-2H-pyrazol-3-yl)-amine (II-37): 1HNMR (500 MHz, DMSO-d6) 5 8.78 (s, br, 1H) , 8.00 (t, J = 7.4 Hz, 1H) , 7.90 (m, 2H) , 7.74 (t, J = 7.5 Hz, 1H) , 7.63 (t, J = 7.3 HZ, 1H), 7.30 (d, J = 8.4 Hz, 1H) , 7.18 (t, J = 7.5 Hz, 1H) , 6.58 (s, br, 1H) , 3.90 (s. 3H) , 2.21 (s, 3H) ; MS 332.1 (M+H). Example 38 [2- (2,6-Dimethylphenyl) -quinazolin-4-yl] - (5- methyl-2H-pyrazol-3-yl)-amine (II-38): 1HNMR (500 MHz, DMSO-d6) 512.2 (s, br, 2H) , 8.88 (d, J ? 7.7 Hz, 1H) , 8.05 (t, J = 7.7 Hz, 1H), 7.80 (m, 2H) , 7.37 (t, J = 7.6 Hz, 1H) , 7.21 (d, J = 7.7 Hz, 2H), 6.36 (s, 1H) , 2.16 (s, 3H), 2.15 (s, 6H); MS 330.1 (M+H). Example 39 [2- (2-Acetylpb.enyl) -quinazolin-4-yl] - (5- metnyl-2H-pyrazol-3-yl)-amine (II-39): 1HNMR (500 MHz, DMSO-d6) 512.35 (s, br, 1H) , 8.93 (d, J = 8.4 Hz, 1H) , 8.37 (d, J = 8.6 Hz, 1H), 8.20 (d, J = 7.6 Hz, 1H), 8.II (t, J = 8.0 Hz, 2H) , 7.89 (m, 2H) , 7.77 (m, 2H) , 6.93 (s, 1H) , 2.33 (s, 3H) , 2.04 (s, 3H). MS 344.1 (M+H). Example 40' [2- (2,3-Dimethylphenyl) -quinazolin-4-yl] - (5- meth.yl-r2H-pyrazol-3-yl)-amine (II-40): 1HNMR (500 MHz, DMSO-d6) 512.6 (s, br, 1H) , 12.1 (s, br, iH) , 8.91 (d, J - 7.7 Hz, IH), 8.14 (t, J = 7.2 Hz, IH), 7.95 (d, J = 8.4 Hz, IH), 7.89 (t, J = 7.7 Hz, IH), 7.58 (d, J = 7.6 Hz, IH) , 7.53 (d, J = 7.0 Hz,' IH) , 7.42 (t, J = 7.6 Hz, IH) , 6.60 (s, IH), 2.43 (s, 3H), 2.35 (s, 3H), 2.32 (s, 3H) ; MS 330.1 (M+H). Examp]a 41 (5-Methyl-2ff-pyrazol-3-yl) - [2- (2- trifluoromethylphenyl) -quinazolin-4-yl] -amine (II-41) : 1HNMR (500 MHz, DMSO-d6) 812.3 {s, 1H) , 10.5 (s, 1H) , 8.77 (d, J = 8.2 Hz, 1H), 7.92 (m, 2H) , 7.85 (in, 3H) , 7.56 (t, J = 8.1 Hz, 1H), 7.67 (t, J = 7.4 Hz, 1H), 6.63 (s, 1H), 2.27 (s, 3H); MS 370.1 (M+H). Example 42 [2- (2-Ethylphenyl) -quinazolin-4-yl] - (5-Methyl- 2H-pyrazol-3-yl) -amine (II-42): 1HNMR (500 MHz, DMSO-d6) 88.80 (tn, 1H) , 8.02 (s, br, 1H) , 7.82' (d, J = 8.4 Hz, 1H) , 7.77 (m, 1H) , 7.62 (d, J = 7.6 Hz, 1H) , 7.54 (m, 1H), 7.41 (m, 2H), 6.40 (s, 1H) , 2.75 (g, J = 7.1 Hz, 2H), 2.17 (s, 3H), 0.99 (t, J = 7.5 Hz, 3H) ; MS 330.1 (M+H) . Example 43 (2-Biphenyl-2-yl-quinazolin-4-yl) - (5-methyl- 2H-pyrazol-3-yl)-amine (II-43): 1HNMR (500 MHz, DMSO-d6) 8 8.76 (d, J = 7.6 Hz", 1H) , 8.04 (m, 1H) , 7.75 (m, 6H) . 7.30 (m, 5H), 5.34 (s, 1H), 2.14 (s, 3H); MS 378.2 (M+H). Example 44 12- (2-Hydroxyphenyl) -quinazolin-4-yl] - (5- Methyl-2B'-pyrazol-3-yl)-amine (II-44): 1HNMR (500 MHz, DMSO-d6) 810.9 (s, br, 1H) , 8.62 (d, J = 8.2 Hz, 1H) , 8.28 (d, J = 7.9 Hz, 1H) , 7.87 (m, 2H), 7.60 (t, J = 7.9 Hz, 1H) , 7.37 (t, J = 7.8 Hz, 1H) , 6.92 (m, 2H) , 6.45 (is, 1H), 2.27 (s, 3H); MS 318.1 (M+H). Example 45 [2-(2-Etnoxyplienyl)-quinazolin-4-yl] - (5- Methyl-2H-pyrazol-3-yl.) -amine (II-45) : ^HNMR (500 MHz, DMSO-d6) 812.1 (s, br, 1H)-, 8.75 (d, J = 8.3 Hz, 1H) , 7.97 (t, J = 7.8 Hz, 1H) , 7.82 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 7.5 Hz, 1H) , 7.70 (t, J = 7.8 Hz, .'lH) , 7.56 (t, J = 7.8 Hz, 1H), 7.22 (d, J = 8.4 lHz, 1H) , 7.12 (t, J = 7.6 Hz, 1H), 6.55 (s, 1H), 4.II (q, J = 6.9 Hz, 2H), 2.16 (s, 3H), 1.22 (t, J = 6.9 Hz, 3H) ; MS 346.1 (M+H). Example 46 [5- (Thiophen-2-yl) -2#-pyrazol-3-yl] - [2- (2- trifluoroaethylphenyl) -quinazolin.-4-yi] -amine (II-46) : 1HNMR.(500 MHz, DMSO-d6) 5 8.04 (d, J = 8.3 Hz, 1H) , 8.05 (dd, J = 7.3, 8.2 Hz, 1H), 7.93 (d, J = S.5 Hz, 1H), 7.81 (m, 5H) , 7.34 (d, J = 5.0 Hz, 1H), 7.25 (m, 1H), 7.00 (m, 1H), 6.87 (s, 1H); MS 438.1 (M+H). Example 47 [4-(Thiophen-2-yl)-Zff-pyrazol-3-yl] -[2-(2- trifluoromethylphenyl) -quinazolin-4-yl] -amine (II-47) : Prepared according to Method B. XHNMR (500MHz, DMSO-d6) 5 6.97 (m, 1H), 7.08 (m, 1H), 7.27 (m, 1H), 7.36 (m, 1H) , 7.66 (m, 2H), 7.77 (m, 3H), 7.83 (m, 1H), 8.00 (m, 1H), 8.18 (s, 1H) , 8.62 (d, J =8.2 Hz, 1H) , 10.7 {br. S, 1H); EI-MS 438.1 (M+H); HPLC-Method A, Rt 2.97 min. Example 48 (4-Phenyl-2ff-pyrazol-3-yl)-[2-(2- trifluorometb.ylpben.yl) -quinazolin-4-yl] -amine (21-48) : Prepared according to Method B. 1HNMR (500MHz, DMSO-d6) 5 7.05 (br. s, 1H), 7.14 (t, J = 7.8 Hz, 1H), 7.25 (m, 3H), 7.43 (m, 2H) , 7.60 (m, 2H) , 7.73 (m, 2H) , 7.80 (d, 1H) , 7.95 (m, 1H), 8.12 (br. s, 1H), 8.60 (m, 1H) , 10.6 (br. S, 1H) ; EI-MS 432.2 (M+H); HPLC-Method A, Rt 3.04 min. Example 49 (5-tejrt-Butyl-2H-pyrazol-3-yl) - [2- (2- trifluoromethyl-phenyl) -guinazolin-4-yl] -amine (II-49) : 1HNMR (500 MHz, DMS0-d6) 8 8.76 (d, J = 8.3 Hz, 1H), 7.94 (m, 2H), 7.75 (m, 4H), 7.70 (t, J = 7.6 Hz, 1H), 6.51 (s, 1H) , 1.16 (s, 9H); MS 412.2 (M+H). Example 50 (5-Pbenyl-2H-pyrazol-3-yl)-[2-(2- trif luoromethylphenyl) - quinazolin- 4 -yl ] - amine (II-50) : ^•HNMR (500MHz, DMSO-d6) 8 7.09 (s, 1H) , 7.36 (td, J = 7.8, 1.1 Hz, 1H) , 7.46 (t, J = 7.8 Hz, 2H) , 7.65 (br. d, J « 8.1 Hz, 2H) , 7.78 (m, 2H) , 7.90 (tn, 4H) , 7.95 (d, J - 7.7 Hz, 1H) , 8.00 (t, J B 7.8 Hz, 1H) , 8.81 (d, J = 8.6 Hz, 1H) , II.29 (br. s, 1H) ; El-MS 432.1 (M+H) ; HPLC-Method A, Rt 3.24 min. Example 51 (4,5-Diphenyl-2ff-pyrazol-3-yl) - [2- (2- trlf luoromethylphcnyl) -guinazolln-4-yl] -amine (II-51) : 1HNMR (500MHz, DMS0-d6) 6 7.13 (m, 1H) , 7.18 (m, 5H) , 7.36 (m, 5H), 7.62 (m, 3H) , 7.73 (m, 2H) , 7.85 (m, 1H), 8.48 (d, J = 8.7 Hz, 1H) , 10.02 (s, 1H) , 13.19 (s, 1H) ; EI-MS 5t)8.2 (M+H); HPLC-Metnod A, Rt 3.39 min. Example 52 (4-Carbaiaoyl-2S-pyrazol-3-yl) - [2-(2- trifluorometh.ylph.enyl) -quinazolin-4-yl] -amlne (II-52) : Prepared in 40% yield. 1HNMR (500MHz, DMS0-d6) : 5 12.85 (s, 1H) , 12.77 (s, 1H) , II.80 (s, 1H) , 10.80 (s, 1H) , 8.35-7.42 (m, 9H) ; MS 399.13 (M+H) HPLC-Method'A, Rt 2.782 min. Example 53 (2J?-Pyrazol-3-yl) - 12- (2- trifluoromethylphenyl) -quinazolin-4-yl] -amine (II-53) : Prepared in 38% yield. 1HNMR (500 MHz, DMSO-d6) 8 12.52 (s, 1H), 10.65 (s, 1H), 8.75 (d,.1H) , 7.91-7.68 (m, BH), 6.87 (s, 1H) . MS: (M+H) 356.17. HPLC-Method A, Rt 2.798 min. Example 54 (5-Hydroxy-2H-pyrazol-3-yl) - [2- (2- trifliioromethylphenyl) -quinazolln-4-yl] -amine (II-54) : Prepared in 36% yield; 1HNMR (500 MHz, DMSO-d6) 5 10.61 (6, 1H), 8.75 (s, 1H), 8.03-7.75 (m, 9H), 5.97 (s, 1H); MS 372.18 (M+H); HPLC-Method A, Rt 2.766 min. Example 55 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-55) : Prepared in 30% yield. ^-HNMR (500 MHz, DMSO-d6) S 12.21 (s, 1H), 10.45 (s, 1H), 8.68 (s, 1H) , 7.89-7.45 (m, 8H) , 6.48 (s, 1H), 0.89 (m, 2H) , 0.62 (s, 2H) . MS 396.18 (M+H) ; HPLC-Method A, Rt 3.069 min. Example 56 (5-Methoxymethyl-2H-pyrazol-3~yl) - [2- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (IX-56) : Prepared in 33% yield; 1HNMR (500 MHz, DMSO-d6) 5 12.51 (s, 1H), 10.48 (s, 1H), 8.60 (s, 1H) , 7.81-7.55 (m, 7H) , 6.71 (s, 1H), 4.28 (s, 2H), 3.18 (s, 3H). MS 400.19 (M+H): HPLC-Metnod A, Rt 2.881 min. Example 57 (lff-indazol-3-yl) - [2- (2-trifluoromethyl- pnenyl)-quinazolin-4-yl]-amine (II-57): Prepared to afford 51 mg (78% yield) as pale yellow solid. 1HNMR (500 MHz, DMSO-d6) 812.7 (s, 1H), 10.4 (s, 1H), 8.55 (d, 1H), 7.81 (t, 1H), 7.71 (d, 1H), 7.61 (d, 1H), 7.58 (t, 1H) , 7.46 (m, 4H) , 7.3-6 (d, 1H) , 7.22 (t, 1H) , 6.91 (t, 1H) ppm; LC-MS (ES+) 406.16 (M+H), (ES-) 404.19 (M-H); HPLC- Method A, Rt 3.00 min. Example 58 (4-Chloro-lH-indazol-3-yl)-[2-(2- trifluoromethyl-phenyl)-quinazolin-4-yl]-amine (II-58): Prepared in DMF (70% yield) as pale yellow solid. XHNMR (500 MHz, DMSO-d6) 613.3 (s, br, 1H) , 10.9 (s, br, 1H), 8.60 (d, 1H) , 7.97 (t, 1H), 7.81 (d, 1H) , 7.75 (t, 1H) , 7.67 (d, 1H), 7.63 (dd, 1H), 7.57 (m, 2H), 7.43 (d, 1H), 7.28 (dd, 1H), 7.08 (d, 1H) ppm; LC-MS (ES+) 440.10 (M+H), (ES-) 438.12. (M-H) ; HPLC-Method A, Rt 3.08 min. Example 59 (5-Fluoro-lH-indazol-3-yl)-[2- (2- trifluoromethyl-pnenyl) -quinazolin-4-yl] -amine (II-59) : Prepared in DMF (34% yield) as pale yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.0 (s, 1H), 10.6 (s, 1H), 8.72 (d, 1H) , 7.99 (t, 1H),7.89 (d, 1H) , 7.79 (d, 1H) , 7.75 (t, 1H), 7.68 (m, 3H) , 7.56 (dd, 1H), 7.39 (d, 1H), 7.28 (t, 1H) ppm; LC-MS (ES+) 424.12 (M+H) , (ES-) m/e= 422.13 (M- H) ; HPLC-Method A, Rt 3.05 min. Example 60 (7-Fluoro-lH-indazol-3-yl)-[2- (2- trifluoromethyl-pnenyl) -quinazolin-4-yl] -amine (II-60) : Prepared in DMF (51% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.4 (s, 1H), 10.6 (s, 1H), 8.68 (d, 1H), 7.95 (t, 1H), 7.85 (d,-lH), 7.72 (m, 2H), 7.63. (m, 2H), 7.58 (m, 1H), 7.43 (d, 1H), 7.18 (dd, 1H), 7.00 (m, 1H) ppm; LC-MS (ES+) 424.II (M+H), (ES-) 422.15 (M-H) ; HPLC- Method A, Rt 3.06 min. Example 61 (5-Methyl-lH-indazol-3-yl)-[2- (2- trifluoromethyl-phenyl) -guinazolin-4-yl] -amine (II-61) : Prepared in DMF (81% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.0 (s, br, 1H) , 8.79 (br, 1H) , 8.II (br, 1H), 7.96 (d, 1H) , 7.82 (m, 5H) , 7.46 (s, 1H), 7.41 (d, 1H) , 7.20 (d, 1H), 2.33 (s, 3H) ppm; MS (ES+) 420.15 (M+H), (ES-) 418.17 (M-H); HPLC-Method A, Rt 3.07 min. Example 62 [2-(2,6-Dichloro-phenyl)-quinazolin-4-yl] -(5- fluoro-lH-indazol-3-yl) -amine (II-62): Prepared in DMF (37% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) ?13.0 (s, 1H), 10.8 (s, 1H), 8.72 (d, 1H), 7.97 (t, 1H), 7.90 (d, 1H), 7.75 (t, 1H), 7.53 (m, 3H), 7.43 (t, 1H) , 7.35 (d, 1H) , 7.23 (t, 1H) ppm; LCMS (ES+) 424.08 (M+H), (ES-) 422.10 (M-H); HPLC-Method A, Rt 3.06 min. Example 63 [2 - (2 -Chloro-pheny 1) -quinazolin- 4 -yl] - (lH- indazol-3-yl) -amine (II-63): Prepared in 91% yield. 1HNMR (500MHz, DMSO-d6) ? 7.06 (t, 1H) , 7.36 (t, 1H) , 7.39 (t, 1H), 7.52 (m, 3H), 7.62 (d, 1H), 7.72 (d, 1H), 7.82 (m, 1H), 7.90 (d, 1H), 8.05 (m, 1H), 8.76 (d, 1H), II.5 (m, 1H), 13.02 (s, 1H); EI-MS 372.1 (M+l); HPLC-Method A, Rt 2.93 min. Example 64 (S-Trifluoromethyl-lH-indazol-3-yl)- 12-(2- trif luoromethyl-pheny 1) -gulnazolin-4-yl] -amine (II-64) : Prepared in DMF (57% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.4 (s, br, 1H), II.4 (br, 1H), 8.72 (d, 1H) , 8.12 (s, 1H), 7.98 (t, 1H) , 7.83 (d, 1H) , 7.76 (d, 1H), 7.73 (dd, 1H), 7.60 (m, 4H), 7.52 (d, 1H) ppm; LC-MS (ES+) 474.12 (M+H), (ES-) 472.17 (M-H); HPLC-Method A, Rt 3.25 min. Example 65 (4-Trifluoromethyl-lH-indazol-3-yl) - [2r (2- trifluoromethyl-pheny 1) -quinazolxn-4-yl] -amine (II-65) : Prepared in DMF (8% yield) as yellow solid. ^HNMR (500 MHz, DMSO-d6) 513.7 (s, br, 1H), II.2 (br, 1H), 8.70 (d, 1H) , 8.05 (s,. 1H), 7.85 (m, 3H) , 7.65 (m, 4H) , 7.51 (m, 2H) ppm; LC-MS (ES+) 474.13 (M+H), (ES-) 472.17 (M-H); HPLC-Method A, Rt 3.15 min. Example 66 [2-(2,6-Dichloro-phenyl)-guinazolin-4-yl] -(Uff- indazol-3-yl)-amine (II-66): Prepared in DMF (30% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 812.9 (s, 1H), II.1 (s, 1H), 8.69 (d, 1H) , 7.95 (t, 1H)., 7.82 (d, 1H) , 7.73 (t, 1H) , 7.56 (d, 1H) , 7.47 (s, 1H) , 7.45 (s, 1H) , 7.39 (m, 2H), 7.26 (t, 1H), 6.92 (t, 1H) ppm; LC-MS (ES+) 406.II (M+H) , (ES-) 404.12 (M-H) ; HPLC-Method A, Rt 3.00 min. Example 67 (lH-indazol-3-yl) - [2- (2-methyl-phenyl) - quinazolin-4-yl] -amine (II-67) : Prepared in 55% yield. 1HNMR (500MHz, DMSO-d6) ? 2-15 (s, 3H) , 7.09 (t, 1H) , 7.26 (d, 1H), 7.31 (t, 1H), 7.39 (t, 1H), 7.42 (m, .1H), 7.55 (d 1H), 7.64 (d, 1H), 7.74 (d, lH),7.89 (m, 1H), 7.96 (d, 1H), 8.10 (m, 1H), 8.81 (d, 1H), 12.0 (m, 1H), 13.18 (s, 1H) ; EI-MS 352.2 (M+l) ; HPLC-Method A, Rt 2.93 min. Example 68 (7-Trifluoromethyl-lH-indazol-3-yl) - [2- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-68) : Prepared in DMF (75% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) ??13.5 (s, br, 1H) , II.2 (s, br, 1H) , 8.68 (d, 1H), 7.97 {t, 1H), 7.92 (d, 1H), 7.82 (d, 1H), 7.74 (t, 1H) , 7.70 (d, 1H) , 7.68 (d, 1H) , 7.64 (m, 2H) , 7.57 (m, 1H) , 7..14 (t, 1H) ppm; LC-MS (ES+) 474.II (M+H), (ES-) 472.14 (M-H) ; HPLC-Method A, Rt 3.24 min. Example 69 (6-Trifluorcmeth.yl-lH-indazol-3-yl) - [2- (2- trif luoromethyl-phenyl) -quinazolin-4-yl] -amine (II-69) : Prepared by Method B in DMF (78% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) ? 13 .4 (s, br, 1H) , II.1 (s, br, 1H), 8.67 (d, 1H), 7.95 (t, 1H) , 7.82 (m, 3H), 7.72 (m, 2H), 7.63 (m, 2H) , 7.57 (t, 1H),7.23 (d, 1H) ppm; LC-MS (ES+) 474.12 (M+H), (ES-) 472.15 (M-H); HPLC-Method A, Rt 3.28 min. Example 70 (5-Nitro-lH-indazol-3-yl) - [2- (2- trifluoromethyl-phenyl)-quinazolin-4-yl] -amine (II-70) : Prepared in DMF (82% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) ?13.6 (s, br, 1H), II.4 (s, br, 1H), 8.75 (s, 1H), 8.72 (d, 1H), 8.09 (dd, 1H), 7.98 (t, 1H), 7.83 (d, 1H), 7.75 (t, 1H), 7.70 (m, 2H), 7.61 (m, 3H) ppm; LC-MS (ES+) 451.14 (M+H) , (ES-) 449.12 (M-H) ; HPLC-Method A, Rt 3.02 min. Example 71 (5,7-Difluoro-lH-iadazol-3-yl)-[2-(2- trifluoromethyl-phenyl)-quinazolin-4-yl]-amine (II-71): Prepared in DMF (60% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.7 (s, br,. 1H) , II.2 (s, br, 1H) , 8.73 (d, 1H), 8.03 (t, 1H), 7.88 (d, 1H), 7.80 (m, 2H), 7.70 (m, 3H) , 7.32 (m, 2H) ppm; LC-MS (ES+) 442.14 (M+H), (ES- ) 440.14 (M-H); HPLC-Method A, Rt 3.II min. Example 72 (4-Pyrrol-l-yl-lH-indazol-3-yl)-[2-(2- trifluoromethyl-phenyl)-quinazolin-4-yl]-amine (II-72) : Prepaxed in DMF (33% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.4 (s, br, 1H), II.0 (s, br, 1H) , 8.53 (d, 1H), 7.98 (t, 1H), 7.75 (m, 4H), 7.62 (m, 2H) , 7.52 (d, 1H), 7.43 (t, iH), 7.05 (d, 1H), 6.80 (s, 2H), 5.61 (s, 2H) ppm; LC-MS (ES+) 471.18 (M+H), (ES-) 469.18 (M- H) ; HPLC-Method A, Rt 3.12 min. Example 73 (5-Amino-lH-indazol-3-yl) - [2- (2- trifluoromethyl-phenyl)-quinazolin-4-yl]-amine (II-73): A solution of compound II-70 (70 mg, 0.16 mmol) in MeOH (2 mL) was treated with Raney Ni until solution was colorless (about 1.5 g Raney Ni was added). After stirring at room temperature for 40 min, the mixture, was filtered through celite, the resulting celite was washed with MeOH (5 times) , and the solvent was evaporated in vacuo to provide a crude product that was then purified by HPLC to give the title compound as a yellow solid (10 mg, 15%) . m.p. 221-223°C; 1HNMR (500 MHz, DMSO-d6) ?13.2 (s, br, 1H) , 10.7 (s, br, 1H) , 9.80 (br, 2H) , 8.68 (d, 1H), 7.97 (t, 1H), 7.87 (d, 1H) , 7.75 (m, 2H), 7.65 (m, 5H) , 7.30 (d, 1H) ppm; MS (ES+) 421.16 (M+H) , (ES-) 419.17 (M-H) ; HPLC-Method A, Rt2.41 rain. Example 74 12- (2-Chloro-phenyl) -quinazolin-4-yl] - (7- fluoro-lH-indazol-3-yl)-amine (II-74): Prepared in DMF (35% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) ?13.7 (s, 1H), II.7 (s, br, 1H), 8.80 (d, 1H) , 8.15 (t, 1H), 7.99 (d, 1H), 7.88 (t, 1H), 7.68 (d, 1H) , 7.60 (m, 2H), 7.53 (t, 1H), 7.46 (t, 1H), 7.25 (dd, 1H), 7.04 (m, 1H) ppm; LC-MS (ES+) 390.16 (M+H); HPLC-Method A, Rt 3.00 min. Example 75 [2- (2-Chloro-phenyl) -guinazolin-4-yl] - (5- fluoro-lH-indazol-3-yl)-amine (II-75): Prepared in DMF. 1HNMR (500 MHz, DMSO-d6) 513.2 (s, 1H) , II.7 (s, br, 1H) , 8.80 (d, 1H), 8.10 (t, 1H) , 7.91 (m, 2H), 7.70 (d, 1H), 7.58 (m, 4H) , 7.50 (t, 1H) , 7.29 (t, 1H) ppm; LC-MS (ES+) 390.17 (M+H); HPLC-Method A, Rt 3.00 min. Example 76 [2- (2-Chloro-phenyl) -quinazolin-4-yl] - (5,7- difluoro-lH-indazol-3-yl) -amine (II-76) : Prepared in DMF (55% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 513.8 (s, 1H) , II.5 (s, br, 1H), 8.76 (d, 1H) , 8.08 (t, 1H), 7.93 (d, 1H) , 7.84 (t, 1H), 7.64 (d, 1H) , 7.55 (d, 1H), 7.50 (t, 1H) , 7.44 (m, 2H), 7.36 (t, 1H) ppm; LC-MS (ES+) 408.15 (M+H), (ES-) 406.17 (M-H); HPLC-Method A, Rt 3.08 min. Example 77 [2- (2-Chloro-phenyl) -quinazolin-4-yl] - (5- trifluoromethyl-lH-indazol-3-yl)-amine (II-77): Prepared in DMF (66% yield) as yellow solid. 1HNMR (500 MHz, DMSO- d6) 8.13.5 (S, 1H), II.4 (s, br, 1H) , 8.79 (d, 1H) , 8.29 (s, 1H), 8.07 (t, 1H), 7.93 (d, 1H) , 7.84 (t, 1H) , 7.72- (d, 1H), 7.63 (d, 2H), 7.53 (d, 1H), 7.48 (t, 1H) , 7.36 (t, 1H) ppm; LC-MS (ES+) : m/e= 440.16 (M+H) ; (ES-) : m/e= 438.18 (M-H); HPLC-Method A, Rt 3.22 min. Example 78 [2-(2-cyano-pnenyl)-quinazolin-4-yl] - (1£T- indazol-3-yl)-amine (II-78).: Prepared in 13% yield. 1H- NMR (500 MHz, DMSO) 8 12.9 (br, 1H) , 10.8 (br, 1H) , 8.73 (br s, 1H), 7.97 (m, 4H) , 7.74 (m, 1H), 7.5 (m, 4H), 7.42 (m, 1H) , 7.08 (m, 1H) ppm; MS (FIA) 363.2 (M+H); HPLC- Method A, Rt 2.971 min. Example 79 (5-Bromo-lH-indazol-3-yl) - [2- (2- . . trifluoromethyl-phenyl) -guinazolin-4-yl] -amine (II-79) : Prepared in DMF (64% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.4 (s, 1H) , II.6 (s, br, 1H) , 8.93 (d, 1H) , 8.21 (t, 1H) , 8.14 (s, 1H) , 8.05 (d, 1H) , 7.95 (m, 4H) , 7.86 (t, 1H), 7.65 (d, 1H), 7.59 (d, 1H) ppm; MS" (ES+) 486.10 (M+H), (ES-) 484.09 (M-H); HPLC-Method A, Rt 3.22 min. Example 80 (6-Cnloro-lH-indazol-3-yl) - [2- (2- trifluoromethyl-phenyl) -guinazolin-4-yl] -amine (II-80) : Prepared in DMF (94% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.1 (s, 1H), II.2 (s, br, 1H) , 8.73 (d, 1H) , 8.03 (t, 1H) , 7.87 (d, 1H) , 7.79 (m, 2H) , 7.73 (m, 2H) , 7.67 (m, 2H) , 7.58 (s,. 1H) , 7.04 (dd, 1H) ppm. LC-MS (ES+) 440.14 (M+H), (ES-) 438.16 (M-H); HPLC-Method A, Rt 3.25 min. Example 81 (7-Fluoro-6-trifluorometbyl-lff-indazol-3-yl) - [2- (2-trifluoromethyl-pb.enyl) -quinazolin-4-yl] -amine (II- 81) : Prepared in DMF (30% yield) as yellow solid. 1HNMR (500MHz, DMSO-d6) ?13.9 (s, 1H),-II.O (s, br, 1H), 8.64 (d, IB), 7.94 (t, 1H), 7.81 (d, 1H) , 7.71 (m, 2H) , 7.60 (m, 4H) , 7.20 (dd, 1H) ppm. LC-MS (ES+) 492.18 (M+H) , (ES-) 490.18 (M-H) ; HPLC-Method A, Rt 3.44 min. E2amElS_B2_{6-Bromo-lH-indazol-3-yl) - [2- (2- triflnoromethyl-phenyl) -quinazolin-4-yl] -amine (II-82) : Prepared in DMF (40% yield) as yellow solid. XHNMR (500 MHz, DMSO-d6) ?13.1 (s, 1H) , II.2 (s, br, 1H) , 8.73 (d, 1H), 8.03 (t, 1H), 7.87 (d, 1H), 7.80 (m, 2H), 7.73 (m, 3H) , 7.67 (m, 1H) , 7.61 (d, 1H) , 7.15 (dd, 1H) ppm; MS (ES+) 486.07 (M+H); HPLC-Method A, Rt 3.28 min. Example 83 [2-(2,4-Bis-trifluoromethyl-phenyl)- quinazolin-4-yl] - (5,7-difluoro-lff-indazol-3-yl) -amine (II-83): Prepared in DMF in 28% yield. 1HNMR (500MHz, MeOH-d4) ? 8.81 (d, J=8.4Hz, 1H), 8.35-8.20 (m, 3H) , 8.19-7.96 (m, 3H), 7.40-7.34 (m, 1H), 7.29-7.14 (m, 1H) ; LC-MS (ES+) 510.14 (M+H); HPLC-Method C, Rt 8.29 min. Example 84 (5,7-Difluoro-lH-indazol-3-yl)-[2-(4-fluoro-2- trifltioromethyl-phenyl) -quinazolin-4-yl] -amine (II-84) : Prepared in 48% yield. 1HNMR (500MHz, MeOH-d4) ? 8.74- 8.63 (m, 1H) , 8.23-8.10 (m, 1H) , 7.99-7.90 (m, 2H) •, 7.89- 7.80 (m, 1H), 7.71-7.61 (m, 1H), 7.61-7.50 (m, 1H), 7.24- 7.15 (m, 1H), 7.14-7.02 (m, 1H); LC-MS (ES+) 460.14 (M+H); HPLC-Method C, Rt 7.59 min. Example 85 [2-(2-Bromo-phenyl)-quinazolin-4-yl]-(5,7- difluoro-lH-indazol-3-yl)-amine (II-85): Prepared in THF (21% yield). 1HNMR (500MHz, MeOH-d4) 88.81 (d, J=8.4Hz, 1H) , 8.35-8.20 (m, 3H) , 8.19-7.96 (tn, 3H) , 7.40-7.34 (m, 1H) , 7.29-7.14 (m, 1H) ; LC-MS (ES+) 510.14 (M+H) ; HPLC- Method C, Rt 8.29 min. Example 86 (5,7-Difluoro-lH-indazol-3-yl) - [2- (5-fluoro-2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-86) : Prepared in THF (26% yield) . 1HNMR (500MHz, MeOH-d4) 8 8.62 (d, J=8.4Hz, 1H) , 8.16-8.02 (m, 1H) , 7.96-7.73 (m, 3H) , 7.59-7.48 (m, 1H), 7.48-7.35 (m, 1H), 7.21-7.09 (m, 1H) , 7.09-6.89 (m, 1H); LC-MS (ES+) 460.16 (M+H); HPLC- Method C, Rt 7.28 min. Example 87 [2- (2,4-Dichloro-phenyl) -quinazolin-4-yl] - (5,7-Difluoro-lH-indazol-3-yl)-amine (II-87): Prepared in THF (16% yield). 1HNMR (500MHz, MeOH-d4) ? 8.81 (d, J=8.4Hz, 1H) , 8.35-8.20 (m, 3H) , 8.19-7.96 (m, 3H) , 7.40- 7.34 (m, 1H), 7.29-7.14 (m, 1H); LC-MS (ES+) 510.14 (M+H); HPLC-Method C, Rt 8.29 min. Example 88 [2- (2-Chloro-5-trifluoromethyl-phenyl)- quinazolin-4-yl] - (5,7-Difluoro-lH-indazol-3-yl) -amine (II-88) : Prepared in THF (33% yield) . 1HNMR (500MHz, DMSO-d6) 8 10.76 (s, 1H), 8.66 (d, J=8.3Hz, 1H), 8.06- 7.84 (m, 3H), 7.81-7.63 (m, 3H), 7.48-7.16 (m, 2H); LC-MS (ES+) 476.16 (M+H); HPLC-Method C, Rt 19.28 min. Example 89 (4-Fluoro-1H-indazol-3-yl)-[2-(2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-89) : Prepared in NMP (79% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) ?13.2 (s, 1H), 10.8 (s, br, 1H) , 8.63 (d, 1H), 7.97 (t, 1H), 7.85 (d, 1H), 7.74 (m, 2H), 7.64 (t, 1H), 7.57 (m, 2H),.7.32 (m, 2H), 6.82 (m, 1H) ppm; LC-MS (ES+) 424.17 (M+H) ; HPLC-Method A, Rt 3.14 min. Example 90 (1H-Indazol-3-yl) - [8-methoxy-2- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-90) : Prepared using THF as solvent to afford the title compound as a TFA salt (23% yield). HPLC-Method A, Rt 2.97 min (95%); 1HNMR (DMSO-d6, 500 MHz) ? 12.9 (1H, bs) , II.0 - 10.7(1H, bs) , 8.2.5 (1H, m) , 7.75-7.50 (8H, s) , 7.30 (1H, m) , 6.90 (1H, m) , 4.0 (3H, s) ; MS (m/z) 436.2 (M+H) . Example 91 (5-Fluoro-lH-indazol-3-yl) - [8-methoxy-2- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-91) : Prepared using TFA as solvent to afford the title compound as a TFA salt (23% yield) . HPLC-Method A, Rt 3.10 min. (99%); 1HNMR (DMSO-d6, 500 MHz): 13.0 (1H, bs) , II.0 - 10.7(1H, bs) , 8.25 (1H, m) , 7.75-7.50 (7H, m) , 7.35 (1H, m), 7.25 (1H, m), 4.0 (3H, s); MS (m/z) 454.2 (M+H) . Example 92 (7-Fluoro-lH-indazol-3-yl) - [8-methoxy-2- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-92) : Prepared using THF as solvent to afford the title compound as a TFA salt (98 mg, 58% yield) . HPLC-Method A, Rt 3.20 min (92%); 1HNMR (DMSO-d6, 500 MHz) ? 13.45 (1H, bs) , II.0 - 10.7 (1H, bs) , 8.25 (1H, m) , 7.75-7.60 (5H, m), 7.50.(1H, m), 7.40 (1H, m) , 7.15 (1H, m), 6.95 (1H, m) 4.0 (3H, s); MS (m/z) 454.2'(M+H). Example 93 (5,7-Difluoro-lH-indazol-3-yl) - [8-methoxy-2- (2-trif luoromethyl-phenyl) -quinazolin-4-yl] -amine (II- 93) : Prepared using THF as solvent to afford the title compound as a TFA salt (36% yield) . HPLC-Method A, Rt 3.27 min. (95%); 1HNMR (DMSO-d6, 500 MHz): 13.65 (1H, bs) , II.0 - 10.7 (1H, bs), 8.22 (1H, m), 7.75-7.60 (5H, m) , 7.40 (1H, m), 7.35 (1H, m), 7.19 (1H, m), 4.0 (3H, s); MS (m/z) 472.2 (M+H) . Example 94 12-(2-Chloro-pyridin-3-yl)-guinazolin-4-yl]- {5,7-Difluoro-1H-indazol-3-yl)-amine (II-94): Prepared in DMF. 1HNMR (500MHz, DMSO-d6) ? 13.62 (br s, . 1H, II.06- 10.71 (m, 1H), 8.16-7.70 (m, 4H), 7.60-7.09 (m, 3H); LC- MS (ES+) 409.14 (M+H) ; HPLC-Method A, Rt 2.89 min. Bxample 95 [2- (2-Chloro-4-nitro-phenyl) -quinazolin-4-yl] - (5,7-dlfluoro-lH-indazol-3-yl) -amine (II-95): Prepared in THF. 1HNMR (500MHz, DMS0-d6) ? 13.35 (s, 1H) , 10.74 (s, 1H) , 8.67 (d, J=8.4Hz, 1H), 8.29 (d, J=2.05Hz, 1H) , 8.18- 8.08 (m, 1H), 8.07-7.60 (m, 4H), 7.53-7.10 (m, 2H). LC- MS (ES+) 453.15 (M+H); HPLC-Method D, Rt 3.63 min. Example 96 [2-(4-Amino-2-chloro-phenyl)-quinazolin-4-yl]- (5,7-Difluoro-lH-indazol-3-yl)-amine (II-96) : A solution of compound II-95 (8mg, 0.018mmol) and tin chloride dihydrate (22mg, O.lmmol) in ethanol (2mL) was heated at 100°C for 24h. The reaction was diluted with EtOAc (lOmL) , washed with IN NaOH solution (2xl0mL) , brine, and dried over anhydrous sodium sulfate to afford the crude product!. Purification was achieved by flash chromatography on silica gel (eluting with 1-3% MeOH in CH2C12.) The title compound was isolated as pale yellow solid (1.2mg, 16% yield). LC-MS (ES+) 423.12 (M+H), HPLC-Method C, Rt 13.78 min. Example 97 (4,5,6,7-Tetrahydro-lH-indazol-3-yl) -[2- (2-trifluoromethyl-phenyl) -guinazolin-4-yl] -amine {II-97) : Prepared in 34% yield. 1HNMR (500MHz, DMSO-d6) ? 1.58 (m, 2H), 1.66 (m, 2H), 2.24 (m, 2H), 2.54 (m 2H), 7.63 (m, 3H), 7.71 (t, 1H) , 7.75. (d, 1H) , 7.78 (d, 1H) , 7.85 (t, 1H), 8.53 (d, 1H) , 9.99 (s, 1H), 12.09 (s, 1H) ; EI-MS 410.2 (M+l) ; HPLC-Method A, Rt 3.05 min. Example 98 (lH-Pyrazolo [4,3-b]pyridin-3-yl) - [2- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-98) : Prepared in OMF (37% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.1 (s, br, 1H) , II.2 (s, br, 1H), 8.73 (d, 1H) , 8.54 (dd, 1H) , 8.12 (d, 1H) , 8.06 (t, 1H) , 7.90 (d, 1H) , 7.84 (t, 1H) , 7.75 (d, 1H), 7.69 (m, 2H) , 7.65 (t, 1H) , 7.47 (dd, 1H) ppm; LC-MS (ES+) 407.18 (M+H); HPLC-Method A, Rt 2.77 min. Example 99 (1H-Pyrazolo [3,4-b]pyridin-3-yl) - [2- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-99) : Prepared in IMF (45% yield) . 1HNMR (500 MHz, DMSO-d6) ?13.5 (s, br, 1H), II.3 (s, br, 1H), 8.78 (d, 1H), 8.49 (d, 1H) , 8.17 (d, 1H) , 8.03 (t, 1H) , 7.89 (d, 1H) , 7.80 (m, 2H), 7.74 (m, 2H) , 7.68 (m, 1H), 7.08 (dd, lH).ppm. MS -(ES+) 407.16 (M+H), (ES-) 405.16 (M-H) ; HPLC-Method A, Rt.2.80 min. Example 100 (6-Methyl-lH-pyrazolo[3,4-b]pyridin-3-yl) - [2- (2-trif luoromethyl-phenyl) -guinazolin-4-yl] -amine (II- 100): Prepared in DMF (II% yield). 1HNMR (500 MHz, DMSO- d6) ?13.2 (s, br, 1H) , 10.8 (s, br, 1H), 8.57 (d, 1H) , 7.95 (t, 1H) , 7.82 (d, 1H) , 7.72 (t, 1H) , 7.65 (m, 2H) , 7.58 (m, 2H) , 2.44 (s, 3H, buried by DMSO) , 2.20 (s, 3H) ppm. LC-MS (ES+) 435.22 (M+H), (ES-) 433.25 (M-H); HPLC- Method A, Rt 2.94 min. Example 101 (6-Oxo-5-phenyl-5,6-dihydro-lH-pyrazolo[4/3- clpyridazin-3-yl) - [2- (2 -trifluoromethyl-phenyl) - quinazolin-4-yl] -amine II-101: Prepared in DMF (6% yield). 1HNMR (500 MHz, DMSO-d6) ?12.6 (s, 1H) , II.0 (s, br, 1H) , 8.60 (d, 1H) , 7.95 (t, 1H), 7.88 (d, 1H), 7.80 (d, 1H), 7.68 (m, 4H), 7.40 (s, 3H), 7.22 (s, 2H) , 6.61 (s, 1H) ppm. LC-MS (ES+) 500.21 (M+H), (ES-) 498.16 (M- H) ; HPLC-Method A, Rt 3.00 min. Example 103 [6-Methyl-2- (2-trifluoromethoxy-ph.enyl) - pyrimidin-4-yl] - (5-phenyl-2H-pyrazol-3-yl) -amine (II- 103): MS 412.13 (M+H); HPLC-Method E Rt 1.248 min. Example 104 (5-Furan-2-yl-2H-pyrazol-3-yl) - [6-methyl-2- (2-trifluorometnoxy-phenyl) -pyrimidin-4-yl] -amine (II- 104); MS. 402.12 (M+H); HPLC-Method E, Rt 1.188 min. Example 105 [6-Ethyl-2- (2-trifluoromethoxy-phenyl) - pyrimidin-4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (II- 105): MS 364.14 (M+H); HPLC-Method E,' Rt 1.II2 min. Example 106 [2- (2-Chloro-phenyl) -pyrido [2,3-d] pyrimidin- 4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (II-106): 1HNMR (500 MHz, DMSO) ?12.23 (s, 1H) , 10.78 (s, 1H) , 7.73-7.47 (m, 7H) , 6.72 (s, 1H) , 2.21 (s, 3H). MS: (M+H) 337.02. HPLC-Method A, Rt 2.783 min. Example 107 (5-Fluoro-lH-indazol-3-yl) - [2- (2- trif luoromethyl-phenyl) - 6,7 -dihydro-5H- cyclopentapyrimidin-4-yl] -amine (II-107) : Prepared in 68% yield. 1HNMR (500MHz, DMSO-d6) ? 2.16 (t, 2H), 2.88 (m, 2H) , 2.98 (t, 2H), 7.21 (td, 1H) , 7.29 (dd, 1H), 7.50 (dd, 1H), 7.65 (t, 1H), 7.67 (t, 1H), 7.73 (t, 1H), 7.79 (d, 1H) , 10.22 (br. S, 1H) , 12.99 (br. s, 1H) ; EI-MS 414.2 (M+H); HPLC-Method A, Rt 2.92 min. Example 108 (1H-Indazol-3-yl)-[2-(2-trifluoromethyl- phenyl) -pyrido[2,3-d]pyrimidin-4-yl] -amine (II-108) : HPLC-Method A, Rt 2.78 min. (95%); 1HNMR (DMSO-d6, 500 MHz): 12.95 (1H, bs) , II.45 5 II.15(1H, bs) , 9.20 (2H, m), 7.85-7.70 (2H, m), 7.70-7.55 (4H, m) , 7.50 (1H, m), 7.35 (1H, m), 7.05 (1H, m); MS (m/z) 407.03 (M+H). Example 109 (5,7-Difluoro-lH-indazol-3-yl) - [2- (2- trifluoromethyl-phenyl) -pyrido [2,3-d]pyrimidin-4-yl] - arnine (II-109) : Yellow, di-TFA salt (25% yield) . HPLC (Method A) 3.10 min. (95%); 1HNMR (DMSO-d6, 500 MHz) : 13.8-13.6 (1H, bs), II.4 - II.2(1H, bs), 9.15 (2H, m), 7.85-7.75 (2H, m) , 7.75-7.62 (3H, m) , 7.32 (2H, m) ; MS (m/z) 442.98 (M+H). Example II0 [2- (2-Chioro-phenyl) -pyrido [2,3-d] pyrimi din - 4-yl] -{1H-indazol-3-yl) -amine (II-II0)i Prepared from 2- aminonicotinic acid and 2-chlorobenzoyl chloride afforded the title compound as a di-TFA salt (28% yield) . HPLC- Method A, Rt 2.85 min. (95%); 1HNMR (DMSO-d6, 500 MHz): 12.90 (1H, s), II.10 - 10.90 (1H, bs), 9.05 (2H, m), 7.75-7.60 (2H, m) , 7.51 (1H, m) , 7.45-7.25 (5H, m) ,6.95 (1H, m); MS (m/z) 372.99(M+H). Example III (5-Fluoro-lH-indazol-3-yl) - [2-(2- trifluoromethyl-phenyl) -5,6,7,8,9,10-heacahydro- eyclooctapyrimidin-4-yl]-amine (II-III). Prepared in 43% yield. 1HNMR (500MHz, DMSO-d6) 8 1.46 (m, 2H) , 1.53 (m, 2H) , 1.77 (m, 4H) , 2.95 (m, 2H) , 3.04 (m, 2H) , 7.22 (m, 2H), 7.50 (dd, 1H), 7.72 (m, 3H) , 7.80 (d, 1H) , 10.5 (m, 1H) , 13.05 (br S, 1H) ; El-MS 456.2 (M+H); HPLC-Method C, Rt II.93 min. Example II2 [2- (2-Chloro-phenyl) -6,7-dihydro-5H- cyclopentapyrimidin-4-yl] - (5-fluoro-1H-indazol-3-yl) - amine (II-II2) : Prepared in 67% yield. 1HNMR (500MHz, DMS0-d6) ?2.18 (m, 2H), 2.89 (m, 2H) , 3.02 (t, 2H) , 7.24 (td, 1H), 7.42 (m, 2H), 7.49 (td, 1H) , 7.52 (dd, 1H) , 7.54 (d, 1H) , 7.57 (dd, 1H) , 10.50 (br. s, 1H) , 13.06 (br. s, 1H) ; EI-MS 380.1 (M+l) ; HPLC-Method C, Rt 9.68 min. Example II3 (lH-Indazol-3-yl) - [2- (2-trifluoromethyl- phenyl) -6,7-dihydro-5H-cyclopentapyrimidin-4-yl] -amine (II-II3) : Prepared in 37% yield. 1HNMR (500MHz, DMSO-d6) 5 2.65 (m, 2H), 2.85 (m, 2H), 2.99 (t, 2H) , 7.02 (t, 1H) , 7.32 (t, 1H), 7.47 (d, 1H), 7.55 (d, 1H), 7.68 (t, 1H) , 7.74 (t, 1H), 7.80 (d, 1H), 10.37 (br. s, 1H) , 12.91 (br. S, 1H); EI-MS 396.1 (M+H); HPLC-Method B, Rt 9-88 min. Example II4 (7-Fluoro-lH-indazol-3-yl)-[2-(2- trifluoromethyl -phenyl) -6,7- dihydro - 5H- cydopentapyrimidin-4-yl]-amine (II-II4): Prepared in 40% yield. 1HNMR (500MHz, DMSO-d6) ? 2.15 (m, 2H) , 2.87 (m, 2H), 2.97 (t, 2H), 6.99 (td, 1H), 7.17 (dd, 1H), 7.38 (d, 1H), 7.65 (m, 2H), 7.71 (t, 1H) , 7.78 (d, 1H), 10.21 (br. S, 1H), 13.40 (br. s, 1H); EI-MS 414.1 (M+H); HPLC-Method C, Rt 9.99 min. Example II5 (5,7-Difluoro-lH-indazol-3-yl) - [2- (2- trifluoromethyl-phenyl) -6,7-dihydro-5H- cyclopentapyrimidin-4-yl]-amine (II-II5): Prepared according to Method C in 52% yield. 1HNMR (500MHz, DMSO- d6) ? 2.16 (m, 2H), 2.89 (m, 2H) , 2.97 (t, 2H),.7.19 (dd, 1H) , 7.29 (td, 1H) , 7.63 (t, 1H), 7.66 (d, 1H), 7.71 (t, 1H), 7.78 (d, 1H), 10.16 (br. s, 1H) , 13.55 (br. s, 1H) ; El-MS 432.1 (M+H); HPLC-Metnod C, Rt 10.09 min. Example II6 [2- (2-Chloro-pnenyl) -6,7-dihydxo-5H- cyclopentapyrimidin-4-yl] - (lH-indazol-3-yl) -amine (II- II6) : Prepared in 56% yield. 1HNMR (500MHz, DMSO-d6) ? 2.16 (m, 2H) , 2.85 (m, 2H) , 3.01 (t, 2H) , 7.06 (t, 1H) , 7.34 (t, 1H), 7.40 (t, 1H), 7.48 (m, 2H) , 7.53 (d, 1H) , 7.56 (d, 1H), 7.63 (d, 1H), 10.39 (br. S, 1H), 12.91 (s, 1H) ; El-MS 362.1 (M+H); HPLC-Method A, Rt 3.09 min. Example II7 [2-(2-Chloro-phenyl)-6,7-dihydro-5H- cyclopentapyrimidin-4-yl] - (7-fluoro-lH-indazol-3-yl) - amine (II-II7) : Prepared in 63% yield. 1HNMR (500MHz, DMSO-d6) ? 2.15 (m, 2H) , 2.87 (m, 2H) , 3.00 (t, 2H) , 7.01 (td, 1H), 7.19 (dd, 1H) , 7.39 (t, 1H) , 7.45 (m, 2H), 7.51 (d, 1H), 7.55 (d, 1H) , 10.35 (br. s, 1H), 13.45 (br. s, 1H) ; EI-MS 380.1 (M+H); HPLC-Method A, Rt Rt 3.15 min. Example II8 [2-(2-Chloro-ph.enyl)-6,7-dihydxo-5H- cydopentapyrimidin-4-yl] - (5,7-difluoro-lH-indazol-3-yl) - amine (II-II8) : Prepared in 60% yield. 1HNMR (500MHz, DMSO-d6) 6 2.18 (m, 2H) , 2.91 (m, 2H) , 3.01 (t, 2H) , 7.32 (t, 1H) , 7.33 (td, 1H) , 7.41 (t, 1H), 7.48 (t, 1H) , 7.53 (d, 1H) , 7.55 (dd, 1H), 10.35 (br. s, 1H), 13.45 (br. s, 1H) ; EI-MS 398.1 (M+H); HPLC-Method A, Rt Rt 3.24 min. Example II9 (lff-Indazol-3-yl) - [2- (2-trifluoromethyl- pbenyl) -S, 6,7, 8,9,10-hexahydro-cyclooctapyrimidin-4-yl] - amine (II-II9) : Prepared in 36% yield. 1HNMR (500MHz, DMSO-d6) 5 1.47 (m, 2H), 1.53 (m, 2H) , 1.78 (m, 4H), 2.96 (m, 2H), 3-06 (t, 2H) , 7.03 (t, 1H), 7.47 (t, 1H), 7.72 (d, 1H) , 7.73 (d, 1H), 7.72 (m, 3H), 7.81 (d, 1H),.1O.52 (m, 1H) ,. 12.97 (br. s, 1H) ; EI-MS 438.2 (M+l) ; HPLC- Method A, Rt 3.37 min. Example 120 (7-Fluoro-lH-indazol-3-yl)-[2- (2- trifluoromethyl-phenyl)-5,6,7,8,9,10-hexahydro- cyclooctapyrimidin-4-yl]-amine (II-120): Prepared in 40% yield. 1HNMR (500MHz, DMSO-d6) ? 1.46 (m, 2H) , 1.52 (m, 2H), 1.77 (m, 4H), 2.94 (m, 2H), 3.04 (m, 2H) , 7.00 (td, 1H), 7.17 (dd, 1H), 7.30 (d, 1H) , 7.70 (m, 3H), 7.79 (d, 1H), 10.5 (m, 1H), 13.49 (br s, 1H); EI-MS 456.1 (M+H); HPLC-Method A, Rt 3.43 min. Example 121 (5,7-Difluoro-lH-indazol-3-yl) - [2- (2- trifluoromethyl-phenyl)-5,6,7,8,9,10-hexahydro- cyelooctapyrimidin-4-yl]-amine (II-121): Prepared in 48% yield. 1HNMR (500MHz, DMSO-d6) ? 1.46 (m, 2H) , 1.52 (m, 2H), 1.77 (m, 4H), 2.95 (m, 2H), 3.03 (m, 2H) , 7.14 (d, 1H) , 7.30 (t, 1H), 7.73 (m, 3H), 7.80 (d, 1H) , 10.5 (m, 1H) , 13.62 (br. S, 1H) ,- EI-MS 475.1 (M+l); HPLC-Method A, Rt 3.52 min. Example 122 [6-Cyclohexyl-2 - (2 -trifluoromethyl-phenyl) - pyrimidin-4-yl] - (lH-indazol-3-yl)-amine (II-122): Prepared in 45% yield. 1HNMR (500 MHz, CDC13) ? 1.30 (2H, m), 1.46 (2H, m), 1.65 (2H, m) , 1.76 (2H, m) , 1.91 (2H, m), 2.61 (1H, br m), 7.08 (1H, t, J=7.4 Hz), 7.27' (1H, d, J=8.0 Hz), 7.35 (1H, t, J= 7.1 Hz), 7.50 (1H, t, J=7.0 Hz), 7.58 (1H, t, J=7.4 Hz), 7.66 (3H, m) , 7.72 (1H, d, J=7.8 Hz), 8.0 (1H, br), 9.87 (1H, br) ppm; HPLC-Method D, Rt 3.57 min; LC-MS 438.17 (M+H) + Example 123 [6-(2-Fluoro-phenyl)-2- (2-trifluoromethyl- phenyl) -pyrimidin-4-yl] - (lH-indazol-3-yl) -amine (IX-123) : Prepared in 8% yield. 1HNMR (500 MHz, CDCl3) 8 7.18 (3H, m) , 7.37 (1H, m), 7.43 (1H, t,. J=7.9 Hz), 7.51 (1H, d, J=7.9 Hz), 7.55 (IE, t, J=7.6 Hz), 7.65 (1H, t, J=7.4 Hz), 7.79 (1H, d, J=7.9 Hz), 7.85 (1H, d, J= 7.6 Hz), 8.19 (2H, m) , 8.70 (1H, d, J= 8.5 Hz) ppm; HPLC-Method D, Rt 4.93.min; LC-MS 450.13 (M+H)+ Example 124 (6-Fluoro-lH-indazol-3-yl) - 12- (2- trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-124) . Prepared in DMF (87% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.0 (s, 1H) , II.1 (s, br, 1H), 8.66 (d, 1H), 7.95 (t, 1H) , 7.80 (d, 1H),.7.72 (m, 2H), 7.62 (m, 4H) , 7.21 (dd, 1H), 6.84 (td, 1H) ppm. LC-MS (ES+) 424.15 (M+H); HPLC-Method A, Rt 3.05 min. Example 125 3- [2~.(2-Tri£luoromethyl-plienyl) -quinazolin-4- ylamino] -lH-indazole-5-carboxylic acid methyl ester (II- 125) : To a solution of compound II-79 (100 mg 0.21 mmol) in DMF (2 mL) was added MeOH (1 mL) , DIEA (54 uL, 0.31 mmol) and PdCl2(dppf) (4 mg, 0,005 mmol). The flask was flushed with CO three times and then charged with a CO balloon. The reaction mixture was heated at 80°C for 14 h then poured into water. The resulting precipitate was collected and washed with water. The crude product was then purified first by flash column (silica gel, 50% • ethyl acetate in hexanes) then by preparative HPLC to to afford II-125 (32%) as yellow solid. 1HNMR (500 MHz, DMSO-d6) 813.3 (s, 1H), II.3 (s, br, 1H) , 8.70 (d, 1H) , 8.36 (s, 1H) , 7.97 (t, 1H) , 7.82 (m, 2H) , 7.71 (m, 3H) , 7.58 (m, 2H) , 7.51 (d, 1H) , 3.75 (s, 3H) ppm; LC-MS (ES+) 464.13 (M+H); HPLC-Method A, Rt 3.12 min. Example 208 (5-Methyl-2H-pyrazol-3-yl) - [2- (2-naphthyl-l- yl) -qu.inazolin-4-yl] -amine (II-208): 1HNMR (500 MHz, DMSO- 6.6) ? 8.92 (s, 1H), 8.73 (m, 1H) , 8.39 (m, 1H) , 8.09 (m, 2H), 7.95 (m, 3H), 7.62 (m, 3H), 6.78 (s, 1H), 2.32 (s, 3H); MS 352.2 (M+H). Example 209 [2- (2-Chloro-phenyl) -pyrido [2,3-d] pyrimidin- 4-yl] - (7-fluoro-lff-indazol-3-yl) -amine (II-214) : Prepared from 4-Chloro-2- (2-cnloro-phenyl) -pyrido[2,3-d]pyrimidine (100 mg, 0.36mmol) and 7-Fluoro-lH-indazol-3-ylamine (108mg, 0.72mmol). Purification by preparative HPLC afforded the title compound as a yellow, di-TFA salt (93 mg, 46% yield). HPLC-Method A, Rt 3.04 min; 1H NMR (DMSO, 500 MHz): ? 13.67 (1H, s), II.40-II.25 (1H, bs), 9.35- 9.25 (2H, m) , 7.95 (1H, m) , 7.80-7.47 (5H, m) , 7.-35 (1H, m) , 7.15 (1H, m); MS (m/z), MH+ 391.1. Example 210 [2- (2-Chloro-pbenyl) -pyrido [2,3-d]pyrimidin- 4-yl] - (5-fluoro-lH-indazol-3-yl)-amine (II-215): Prepared from 4-Chloro-2- (2-chloro-phenyl) -pyrido[2,3-d] pyrimidine (100 mg, 0.36mmol) and 5-Fluoro-lJ?-indazol-3- ylamine (108mg, 0.72mmol). Purification by preparative HPLC afforded the title compound as a yellow, di-TFA salt (45 mg, 22% yield). HPLC-Method A, Rt 3.00 min; XH NMR (DMSO, 500 MHz): 8 13.0 (1H, s) , 10.90 (1H, bs) , 9.15-9.05 (2H, m) , 7.70 (1H, m) , 7.60-7.30 (6H, m), 7.20 (1H, m); MS (m/z), MH* 391.1. Example 2II [2- (2-Chloro-phenyl) -pyrido [2,3-d]pyrimidin- 4-yl] - (5,7-di£luoro-lH-indazol-3-yl) -amine (II-216) : Prepared from 4-Chloro-2-(2-chloro-phenyl)-pyrido [2, 3- d]pyrimidine (100 mg, 0.36mmol) and 7-Difluoro-1H- indazol-3-ylamine, (II2mg, 0.66mmol) . Purification by preparative HPLC afforded the title compound as a yellow, di-TFA salt (130 mg, 62% yield). HPLC-Method A, Rt 3.12 min; lH NMR (DMSD, 500 MHz): 13.80-13.60 (1H, bs) , II.30- II.10 (1H, bs), 9.20-9.10 (2H, m) , 7.80 (1H, m), 7.60- 7.30 (6H, m); MS (m/z) , MH4 409.1. Example 212 [2- (2-Chloro-ph.enyl) -pyr±do[3,4-d]pyrimidin- 4-yl]- (lff-indazol-3-yl)-amine (II-217): Prepared from 4- C!hloro-2- (2-chloro-phenyl) -pyrido [3, 4-d] pyrimidine (100 mg, 0.36mmol) and lH-indazol-3-ylamine (88mg, 0.66mmol) Purification by preparative HELC afforded the title compound as a yellow, di-TFA salt (72 mg, 33% yield) . HPLC-Method A, Rt 3.21 min;. ^H NMR (DMSO, 500 MHz) : 8 12.95 (1H, s), 10.90 (1H, bs), 9.25 (1H, s), 8.75 (1H, m), 8.55 (1H, m) , 7.65 (1H, m), 7.55 (1H, m), 7.50-7.30 (5H, m) , 7.00(1H, m) ; MS (m/z), MH+ 373.1. Example 213 [2- (2-Cliloro-phenyl) -pyridoI3,4-d]pyrimidin- . 4-yl] - (7-fluoro-lff-inda2ol-3-yl)-amine (II-218): Prepared from 4-Chloro-2- (2-chloro-phenyl) -pyrido [3,4-d]pyrimidine (100 mg, 0.36mmol) and 7-Fluoro-lH-indazol-3-ylamine (108mg, 0.72mmol). Purification by preparative HPLC afforded the title compound as a yellow, di-TFA salt (48.7 mg, .22% yield). HPLC-Method A, Rt 3.35 min; B. NMR (DMSO, 500 MHz): 5 12.95 (1H, s) , 10.90 (1H, bs) , 9.25 (1H, s), 8.75 (1H, m) , 8.55 (1H, m) , 7.70-7.35 (5H, m) , 7.25(1H, m) , 6.95 (1H, m) , ; MS (m/z), MH+ 391.08. Example 214 [2- (2-Chloro-phenyl) -pyrido [3,4-d]pyrimidin- 4-yl]-(5-fluoro-lH-indazol-3-yl) -amiae (II-219) : Prepared from 4-chloro-2- (2-chloro-5-fluoro-lH-indazol-3-ylamine (108mg, 0.72mmol). Purification by preparative HPLC. afforded the title compound as a yellow, di-TFA salt (57.2 mg, 26% yield) . HPLC-Method A, Rt 3.27 min; 1H NMR (DMSO, 500 MHz): ? 13.05 (1H, s), 10.95 (1H, s), 9.25 (1H, s), 8.75 (1H, m) , 8.55 (1H, m) / 7.60 (1H, m), 7.55 (1H, m) , 7.50-7.30 (5H, m) , 7.25 (1H, m) ; MS (m/z) , MH+ 391.1. Example 215 [2 - {2 -Chloro-pheny 1) -pyrido [3,4- d] pyr imidin- 4-yl] - (5,7-difluoro-lff-indazol-3-yl) -amine (II-220) : Prepared from 4-chloro-2- (2-chloro-7-difluoro-lH-indazol- 3-ylamine (II2mg, 0.66mmol). Purification by preparative HPLC afforded the title compound as a yellow, di-TFA salt (57.2 mg, 26% yield). HPLC-Method A, Rt 3.45 min; 1H NMR (DMSO, 500 MHz): ? 13.65 (1H, s), II.0 (1H, s), 9.25 (1H, s) , 8.80 (1H, m) , 8.50 (1H, m) , 7.60 (1H, m) , 7.55 (1H, m), 7.50-7.30 (5H, m); MS (m/z), MH+ 409.1. Example 216 6-Fluoro-lH-indazol-3-ylamine (Al) : 1HNMR (500 MHz, DMSO-d6) ?II.4 (s, 1H) , 7.68 (dd, 1H) , 6.95 (dd, 1H), 6.75 (td, 1H), 5.45 (s, 2H) ppm; LC-MS (ES+) 15-2.03 (M+H) ; HPLC-Method A, Rt 2.00 min. Example 217 5-Fluoro-lH-indazol-3-ylamine (A2) : 1HNMR (500 MHz, DMSO-d6) 8II.3 (s, 1H) , 7.43 (d, 1H) , 7.22 (m, 1H) , 7.08 (m, 1H) , 5.29 (s, 2H) ppm; LC-MS (ES+) 152.01 (M+H); HPLC-Method A, Rt 1.93 min. Example 218 5,7-Difluoro-lH-indazol-3-yl-anine (A3) : 1HNMR (500 MHz, CD3OD) ?7.22 (dd, J=2.0, 8.45HZ, 1H) , 7.04-6.87 (m, 1H) ; LC-MS (ES+) 169.95 (M+H); HPLC-Method C, Rt 2.94 min Example 219 7-Fluoro-lH-indazol-3-ylamine (A4) : 1HNMR (500 MHz. DMSO-d6) ?II.8 (s, 1H) , 7.42 (d, 1H) , 6.97 (m, 1H) , 6.78 (m, 1H) , 5.40 (s, 2H) ppm;- LCMS (ES+) 152.01 (M+H) ; HPLC-Method A, Rt 2.00 min. Example 220 7 -Fluoro- 6-trifluoromethyl - 1H-indazol- 3 - ylamine (A5) : 1H-NMR (500 MHz, DMSO) 5 12.5 (s, 1H), 7.75 (d, 1H) , 7.25 (m, 1H) , 5.85 (m, 1H) ppm; MS (FIA) 220.0 (M+H); HPLC-Method A, Rt 2.899 min. Example 221 6-Bromo-lH-indazol-3-yleuiLine (A6) : 1H-NMR (500 MHz, DMSO) ? II.5 (s, 1H) , 7.65 (d, 1H) , 7.40 (s,. 1H) , 7.00 (d, 1H) , 5.45 (br S, 1H) ppm; MS . (FIA) 213.8 (M+H); HPLC-Method A, Rt 2.441 min. Example 222 4-Fluoro-lH-indazol-3-ylamine (A7) : 1H-NMR (500MHz, DMSO) ? II.7 (s, 1H), 7.17 (m, 1H), 7.05 (d, 1H) , 6.7 (br, 1H), 6.60 (dd, 1H), 5.20 (br s, 2H) ppm; MS (FIA) 152.0 (M+H); Method A, Rt 2.256 min. Example 223 5-Bromo-lH-indazol-3-ylamine (A8) : 1H-NMR (500 MHz, DMSO) 8 II.55 (br s, 1H) , 7.95 (s, 1H) , 7.30 (d, 1H), 7.20 (d, 1H) , 5.45 (br s, 2H) ppm; MS (FIA) 213.8 (M+H); Method A, Rt 2.451 min. Example 224 5-Nitro-1H-indazol-3-ylamine (A9) : 1H-NMR (500 MHz, DMSO-d6) 8 9.00 (s, 1H) , 8.20 (d, 1H), 7.45 (d, 1H), 6.15 (br s, 1H) ppm; Method A, Rt 2.184 min Example 225 4-Pyrrol-1-yl-lH-indazol-3-ylamine (A10) : XH- NMR (500 MHz, DMSO) 8 7.20 (s, 2H) , 7.00 (s, 2H), 6.75 (m, 1H), 6.25 (s, 2H), 4.30 (d, 1H) ppm; Method A, Rt 2.625. min. Example 226 4-Cnloro-5,6-dimethyl-2- (2-trifluoromethyl- phenyl) -pyrimidine (Bl) : Prepared to afford a colorless oil in 75% yield. 1H-NMR (500 MHz, CDC13) 8 7.70 (d, J=7.8 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.55 (t, J=7.6 Hz, 1H) , 7.48 (t, J=7.5 Hz, 1H) , 2.54 (s, 3H) , 2.36 (s, 3H) ppm; MS (FIA) 287.0 (M+H) ; HPLC-Method A, Rt 3.891 min. Example 227 4-Cnloro-2- (2-chloro-phenyl) -5, 6-dimethyl- pyrimidine (B2) : Prepared to afford a yellow-orange oil in 71% yield. ^-NMR (500 MHz, CDC13) 5 7.73 (m, 1H) , 7.52 (m, 1H) , 7.39 (m, 2H), 2.66 (s, 3H) , 2.45 (s, 3H) ppm; MS (FIA) 253.0 (M+H); HPLC-Method A, Rt Rt 4.156 min. Example 228 4-Chloro-6-methyl-2-(2-trifluorometby1- plxenyl)-pyrimidine (B3) : Prepared to afford a pale yellow oil in 68% yield. aH-NMR (500 MHz, CDC13) 5 7.72 (d, J=7.8 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 7.52 (t, J=7.8 Hz, 1H), 7.16 (s, 1H) , 2.54 (s, 3H) ppm; MS (FIA) 273.0 (M+H); HPLC-Method A, Rt 3.746 min. Example 229 4-Cnloro-6-cyclohexyl-2- (2-trifluoromethyl- phenyl) -pyrimidine (B4) : Prepared to afford a yellow oil in 22% yield. ^-NMR (500 MHz, CDC13) 8 7.70 (m, 2H) , 7.57 (t, J=7.5 Hz, 1H) , 7.50 (tt J=7.5 Hz, 1H), 7.19 (s, 1H), 2.65 (m, 1H), 1.9 (m, 2H), 1.8 (m, 2H), 1.5 (m, 2H) , 1.3 (m,-2H), 1.2 (m, 2H) ppm; MS (FIA) 341.0 (M+H). Example 230 4-Cnloro-6-pnenyl-2-(2-trifluoromethyl- phenyl) -pyrimidine (B5) : Prepared to afford a yellow oil in 53% yield. '"H-NMR (500 MHz, CDC13) 8 8.08 (dd, J=7.9, 1.6 Hz, 2H) , 7.80 (d, J=7.6 Hz, 1H), 7.77 (d, J=7.8 Hz, 1H) , 7.67 (s, 1H) , 7.61 (t, J=7.5 Hz, 1H) , 7.54 (t, J=7.6 Hz, 1H), 7.47 (m, 3H) ppm; MS (FIA) 335.0 (M+H) ; HPLC- Method A# Rt 4.393 min. Example 231 4-Chloro-2- (2,4-dichloro-phenyl) -5,6- dimethyl-pyximidine (B6) : Prepared to afford a white solid in 91% yield. ^-NMR (500 MHz, CDC13) 5 7.62 (d, J=8.3 Hz, 1H), 7.43 (d, J=7.0 Hz, 1H), 7.27 (dd, J=8.3, 2.0 HZ, 1H) , 2.55 (s, 3H), 2.35 (s, 3H) ppm; MS (FIA) 287, 289 (M+H); HPLC-Method A, Rt 4.140 min. ExaaQjle_23_2_ 4-Cliloro-6- (2-chloro-phenyl) -2- (2- trifluorometbyl-phenyl)-pyrimidine (B7) : Prepared to affod a yellow oil in -52% yield. ^-NMR (500 MHz, CDC13) 5 7.75 (m, 3H), 7.65 (m, 2H), 7.53 (m, 1H), 7.44 (m, 1H), 7.36 (m, 2H) ppm; MS (FIA) 369.1 (M+H); HPLC-Method A, Rt 4.426 min. Example 233 4-Ch3oro-6-(2-fluoro-phenyl)-2-(2- trifluoromethyl-phenyl) -pyrimidine (B8) : Prepared to afford a yellow oil in 95% yield. ^fl-NMR (500 MHz, CDC13) 5 8.24 (t, J=7.9 Hz, 1H), 7.84 (s, 1H) , 7.78 (d, J=7.7 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.60 7.53 (t, J=7.6 Hz, 1H) , 7.43' (m) 1H), 7.23 (t, J=7.6 Hz, 1H) , 7.13 (m, 1H) ppm; MS (FIA) 353.0 (M+H). Example 234 4-Chloro-6-pyridixi-2-yl-2-(2-trifluoromethyl- phenyl) -pyrimidine (B9) : Prepared to afford a pale yellow solid in 50% yield: ^-NMR (500 MHz, CDC13) 8 8.68 (m, 1H) , 8.48 (dd, J=7.9,-0.8 Hz, 1H), 8.38 (d, J=2.3 Hz, 1H) , 7.84 (m, 3H), 7.62 (t, J=7.6 Hz, 1H), 7.55 (t, J=7.6 Hz, 1H), 7.38 (m, 1H) ppm; MS (FIA) 336.0 (M+H); HPLC- Method A, Rt 4.575 min. Example 235 6-Benzyl-4-chloro-2- (2-trifluoromethyl- phenyl) -5, 6,7, 8-tetrahydro-pyrido [4,3-d]pyrimidine (BIO) : 1HNMR (500 MHz, CDC13) 5 7.. 70 (d, 1H) , 7.62 (d, 1H) , 7.55 (t, 1H), 7.48 (t, 1H), 7.32 (m, 4H), 7.25 (m, 1H) , 3.74 (s, 2H), 3.66 (s, 2H), 2.99 (t, 2H), 2.80 (t, 2H) ppm; LCMS (ES+) 404.17 (M+H) ; HPLC-Method A, Rt 3.18 min. Example 236 7-Benzyl-4-chloro-2- (2-trifluoromethyl- phenyl)-5,6,7,8-tetrahydro-pyrido [3,4-d]pyrimidine (Bll) : 1HNMR (500 MHZ, CDC13) 8 7.69 (d, 1H) , 7.60 (d, 1H) , 7.54 (t, 1H), 7.47 (t, 1H), 7.28 (m, 4H), 7.20 (m, 1H) , 3.68 (s, 2H), 3.67 (s, 2H), 2.86 (t, 2H) , 2.79 (t, 2H) ppm. MS (ES+) 404.18 (M+H); HPLC-Method A, Rt 3.12 min. Example 237 4-Cliloro-2- (4-£luoro-2-trifluoromethyl- phenyl)-guinazoline (B12) : 1HNMR (500MHz, CD3OD) 5 8.43 (d, J=8.1Hz, 1H) , 8.20-8.05 (m, 2H), 8.05-7.82 (m, 2H), 7.71-7.51 (m, 2H) . LC-MS (ES+) 327.09 (M+H). HPLC-Method D, Rt 4.56 min. Example 238 4-Chloro-2- (2-ehloro-5-trif luoromethyl- phenyl)-guinazoline (B13): LC-MS (ES+) 342.97 (M+H). HPLC-Method D, Rt 4.91 min. Example 23 9 4-Chloro-2- (2-cliloro-4-nitro-phenyl) - quinazoline (B14) : LC-MS (ES+) 319.98 (M+H). HPLC-Method D, Rt 4.45 min. Example 240 4-Chloro-2- (2-trifluoromefchyl-phenyl) - guinazoline (B15) : Prepared in 57% yield. White solid. 1HNMR (500MHz, DMSO-d6) 8 7.79 (t, 1H) , 7.86 (t, 1H) , 7.94 (m, 3H) , 8.15 (dd, 1H)., 8.20 (td, 1H) , 8.37 (m, 1H) ; EI- MS 308.9 (M). Example 241 4-Chloro-2-(2-trifluoromethyl-phenyl) - 6,7 - dihydro - SB- cyelopentapyr i mi dine (B16) : Prepaxed in 22% yield. 1HNMR (500MHz, DMSO-d6) 8 2.19 (m, H) , 3.01 (t, 2H), 3.08 (t, 2H), 7.49 (t, 1H), 7.55 (t, 1H), 7.62 (d, 1H), 7.71 (d, 1H). EI-MS 299.0 (M+H). Example 242 4-Chloro-2- (2-cliloro-phenyl) -6,7, 8,9- tetrahydro-EH-cycloheptapyrimidine (B17) : Prepared according to Method C in 82% yield to afford a white solid. 1HNMR (500MHz, CDC13) 8 1.67 (m 4H) , 1.87 (m 2H) ,, 3.02 (m 4H), 7.28 (m, 2H), 7.40. (1, 1H), 7.65 (m, 1H); EI-MS 293.0 (M+l). Example 243 4-Chloro-2- (2 -trif luoromethyl -phenyl) - 5, 6,7, 8,9,10-hexahydro-cyclooctapyrimidine (B18) : Prepared in 38% yield to afford a brown oil. 1HNMR (500MHz, CDCI3) 8 1.35 (m 2H) , 1.41 (m 2H) , 1.76 (m 4H) , 2.96 (m, 4H), 7.48 (t, 1H), 7.56 (t, 1H),.7.66 (d, 1H), 7.70 (d, 1H) ; EI-MS 341.0 (M+l). Example 244 4-Chlbro-8-methoxy-2- (2-trifluoromethyl- phenyl)-guinazoline (B19) : Prepared from 8-methoxy-2-(2- trif luoromethyl-phenyl) -3H-quinazolin-4-one (1. Og, 3.12mmol), triethylamine hydrochloride (472mg, 3.43mmol), and POCI3. Purification by flash chromatography afforded a white solid (89% yield) . HPLC-Method A, Rt 4.10 min, (98%), MS (m/z) 258.08 (M+H). Example 245 2- (4-Chloro-c[uinazplin-2-yl) -benzonitrile (B20) : Prepared to afford a yellow solid in 1.5% yield. ^-NMR (500 MHz, CDC13) 5 8.47 (d, 1H), 8.24 (d, 1H), 8.16 (d, 1H) , 8.07 (impurity), 7.94 (t, 1H) , 7.92 (impurity), 7.86 (d, 1H), 7.68 (m, 2H), 7.65 (impurity), 7.54 (impurity), 7.49 (t, 1H) , 4.2 (impurity), 1.05 (impurity) ppm; MS (LC/MS) 266.05 (M+H) ; HPLC-Method A, Rt 3.88 min. Example 246 6-Methyl-2-(2-trifluorometliyl-phenyl)-3H- pyrimidin-4-one (D3): Prepared to afford a yellow solid in 50% yield. ^H-NMR (500 MHz, DMSO-d6) 8 12.7 (br s, 1H), 7.9 (m, 1H), 7.8 (m, 2H), 7.7 (m, 1H), 6.3 (s, 1H) , 2.21 (s, 3H) ppm; MS (FIA) 255.0 (M+H); HPLC-Method A, Rt 2.578. min. Example 247 6-Cyclohexyl-2- (2-trif luoromethyl-phenyl) -3H- pyrimidin-4-one (D4): Prepared to afford an off-white solid in 54% yield. ^-NMR (500 MHz, DMSO-d6) 8 12.9 (br s, 1H), 7.9 (m, 4H), 6.3 (s, 1H), 2.5 (m, 1H), 1.9 (m, 5H) , 1.4 (m, 5H) ppm; MS (FIA) 323.1 (M+H); HPLC-Method A, Rt 3.842 min. Example 248 2- (2-Chloro-5-trifluorometh.yl-phenyl) -3H- quinazoli-4-one (D10): XHNMR (500MHz, CD3OD) 8 8.32-8.25 (m, 1H), 8.01 (s, 1H), 7.91-7.72 (m, 1H) , 7.66-7.55 (m, 1H) . LC-MS (ES+) 325.01 ' (M+H) . HPLC-Method D, Rt 3.29 min. Example 249 2-{4-Fluoro-2-trifluoromethyl-phenyl)-3H-r qainazolin-4-one (D14) : ^-HNMR (500MHz, CU3OD) 8 8.28 (d, 8.0HZ, 1H) , 7.94-7.84 (m, 1H) , 7.84-7.77 (m, 1H), 7.76- 7.67 (in, 2H), 7.65-7.53 (m, 2H) . LC-MS (ES+) 309.06 (M+H). HPLC-Method D,Rt 2.88 min. Example 250 2-(4-Nitro-2-chloro-phenyl)-3H-quinazolin-4- one (D15): LC-MS (ES+) 302.03 (M+H). HPLC-Method D, Rt 2.81 min. Example 251 2- (5-Fluoro-2-trif luorome thyl-phenyl) -3ff- quinazolin-4-one (D17) : XHNMR (500MHz, CD3OD) 8 8.28 (d, Rt J=8.05Hz, 1H), 7.96 (dd, J=5.05, 8.55HZ, 1H), 7.89 (t, J=7.9Hz, 1H) , 7.78-7.69 (m,lH), 7.66-7.46 (m, 3H). LC-MS (ES+) 309.14 (M+H) . HPLC-Method D, Rt 2.90 min. Example 252 (lH-Indazol-3-yl) - (2-phenyl-quinazolin-4-yl) - amine (III-l) : Prepared by Method A in DMF to afford 70. mg (50% yield) as pale yellow solid. XK NMR (500 MHz, DMSO-d6) 513.1 (s, br, 1H) , 8.48 (d, 1H), 7.91 (d, 2H) , 7.76 (br, 2H), 7.45 (m, 2H), 7.36 (d, 1H), 7.20 (m, 4H) , 6.86 (t, 1H) ppm. MS (ES+) 338.07 (M+H); (ES-) 336.II (M- H) ; HPLC-Method A, Rt 2.88 min. Example 253 (5-Methyl-2H-pyrazol-3-yl) - (2-phenyl-5, 6,7, 8- tetrahydroquinazolin-4-yl) -amine (III-7) : Prepared according to Method A. H NMR (500 MHz, DMSO-d6) S12.1 (s, br, 1H), 8.70 (s, br, 1H), 8.37 (d, J = 6.7 Hz, 2H), 7.54 (m, 3H), 6.67 (s, 1H), 2.82 (m, 2H), 2.68 (m, 2H) , 2.37 (s, 3H), 1.90 (s, br, 4H) ; MS 306.1 (M+H). Example 254 (5-Methyl-2H-pyrazol—3-yl) - (2-phenyl-6,7, 8,9- tetrahydro-5ff-cyeloheptapyrimidin-4-yl) -amine (III-8) : MS 320.48 (M+H); HPLC-Method E, Rt 1.124 min. Example 255 (5-Methyl-2H-pyrazol-3-yl) - (2-pyridin-4-yl- qu.inazolin-4-yl)-amine (III-9) : Yellow solid, rap 286- 289°C, ^-H NMR (DMSO) S 2.35 (3H, s), 6.76 (1H, s) , 7.61 (1H, m), 7.89 (2H, m) , 8.32 (2H, d) , 8.70 (1H, d) , 8.78 (2H, d), 10.56 (1H, br s), 12.30 (1H, br s) ; IR (solid) 1620, 1598, 1571, 1554, 1483, 1413, 1370, 1328; MS 303.2 • (M+H)+ Example 256 (7-Chloro-2-pyridin-4-yl-quinazolin-4-yl) - (5- methyl-2H-pyrazol-3-yl) -amine (III-28) : 2H NMR (DMSO-d6) 5 2.35 (3H,s), 6.75 (1H, s) ,. 7.65 (1H, d) , 7.93 (1H, s) , 8.30 (2H, d), 8.73 (1H, d), 8.79 (2H, d) , 10.69 (1H, s) , 12.33 (1H, s) ;. MS m/z 337.2 (M+H)+. Example 257 (6-Chloro-2-pyridin-4-yl-quinazolin-4-yl)- (5- methyl-2H-pyrazol-3-yl) -amine (III-29) : ^H NMR (DMSO-d6) 5 2.31 (3H, a); 6.74 (lH,s), 7.89 (1H, s) , 8.30 (2H, d) , 8.80 (2H, d) , 8.91 (1H, s) , 10.63 (1H, s) , 12.29 (1H, s) ; MS 337.2 (M+H)+. Example 258 (2-Cydohexyl-quinazolin-4-yl)-(5-methyl-2H- pyrazol-3-yl)-amine (III-30) : JH NMR (DMSO) 6 2.35 (3H, s), 1.70 (3H, m), 1.87 (2H, d), 1.99 (2H, d), 2.95 (1H, t), 6.72 (1H, s), 7.75 (1H, d), 7.88 (1H, s) , 7.96 (1H, s) , 8.83 (1H, s) , II.95 (1H, s) , 12.70 (1H, s) ; MS 308.4 (M+H) + . Example 259 (5-Methyl-2H-pyrazo 1 -3 -yl) - (2-phenyl- quinazolin-4-yl)-amiae (III-31) : mp 246°C; lH NMR (400MHz) 5 2.35 (3H, s), 6.70 (1H, br s), 7.51-7.57 (4H, mj, 7.83- 7.84 (2H, d) , 8.47-8.50 (2H, d), 8.65 (1H, d) , 10.4 (1H, s), 12.2 (1H, bs); IR (solid) 369«, 3680, 2972, 2922, 2865; MS 302.1 (M+H)+. Example 260 [2-(4-Iodophenyl)-quinazolin-4-yl]-(5-methyl- 2H-pyfazol-3-yl)-amine (III-32) : XH 3SIMR (DMSO-d6) 5 2.34 (3H, s), 6.72 (1H, s), 7.56 (1H, d), 7.84 (2H, d), 7.93 (2H, d) , 8.23 (2H, d) , 8.65 (1H, s) , 10.44 (1H, s) , 12.24 (1H, s); MS 428.5 (M+H)+. Example 261 [2- (3,4-Dichlorophenyl) -quinazolin-4-yl] - (5- methyl-2H-pyrazol-3-yl) -amine (III-33) : A suspension of 2- (3,4-dichloro-phenyl) -3H-quinazolin-4-one (1g, 3.43 mmol) in phosphorus oxychloride (4 inL} was stirred at II0°C for 3 hours. The solvent was removed by evaporation and the residue is treated carefully with cold aqueous, saturated NaHCO3. The resulting solid was collected by filtration and washed with ether to afford 4-chloro-2- (3,5-dichloro-phenyl) -quinazoline as a white solid (993 mg, 93%). To the above compound (400mg, 1.29 mmol) in THF (30 mL) was added 3-amino-5-methyl pyrazole (396 mg, 2.58 mmol) and the resulting mixture heated at 65°C overnight. The solvents were evaporated and the residue triturated with ethyl acetate, filtered, and washed with the minimum amount of ethanol to afford compound III-33 as a white solid (3II mg 65%) -. mp 274°C; XK NMR (DMSO) 5 2.34 (3H, s), 6.69 (1H, s), 7.60 (1H, m), 7.84 (1H, d) , 7.96 (2H, d) , 8.39 (1H, dd) , 8.60 (1H, d) ,' 8.65 (1H, d) , 10.51 (1H, s), 12.30 (1H, s); IR (solid) 1619, 1600, 1559, 1528, 1476, 1449, 1376, 1352, 797, 764, 738; MS 370.5 (M+H)+. Example 262 [2- (4-Bromophenyl)-quinazolin-4-yl]-(5- methyl-2H-pyrazol-3-yl)-amine (III-34): mp 262-265°C; aH NMR (DMSO) 5 2.34 (3S, s), 6.73 (1H, s) , 7.55 (1H, m) , 7.74 (2H, d),.7.83 (2H, m) , 8.40 (2H, d), 8.65 (1H, d) , 10.44 (1H, s) , 12.25 (1H, S.) ; IR (solid) 1603, 1579, 1546, 1484, 1408, 1365; MS 380.1/382.1 (M+H)+. Example 263 [2-(4-Chlorophenyl)-quinazolin-4-yl]-(5- methyl-2H-pyrazol-3-yl)-amine (IIX-35) : mp >300°C; 1H NMR (DMSO) 8 2.34 (3H, s), 6.74 (1H, s), 7.53-7.62 (3H, m) , 7.84 (2H, d), 8.47 (2H, d), 8.65 (1H, d), 10.44 (1H, s) , 12.26 (1H, s) ; IR (solid) 1628, 1608, 1584, 1546, 1489, 1408, 1369., II69; MS 336.2 (M+H) + . Example 264 [2- (3,5-Dichlorophenyl) -guinazolin-4-yl] - (5- metbyl-2Jy-pyrazol-3-yl)-amine (III-36) : mp 228°C; 1H NMR (DMSO) ? 2.34 (3H, s) , 6.69 (1H, s) , 7.96 (1H, d) , 8.21 (3H, m), 8.56 (1H, d) , 8.60 (2H, d) , 10.51 (1H, s), 12.30 (1H, S) ; IR (solid) 1546, 1331, 802, 763, 729, 658, 652; MS 370.5 (M+H)+. Example 265 [2- (4-Cysnophenyl) -quinazolin-4-yl] - (5- methyl-2H-pyrazol-3-yl)-amine (III-37) : mp 263°C; lH NMR (DMSO) 8 2.34 (3H, s) , 6.72 (1H# s) , 7.61 (1H, d), 7.88 (2H, S), 8.04 (2H, d) , 8.63 (2H, d) , 8.67 (1H, s), 10.52 (1H, S), 12.27 (1H, s) ; IR (solid) 1739, 1436, 1366, 1229, 1217; MS 327.2 (M+H)+. Example 266 [2- (3-Iodophenyl) -guinazolin-4-yl] - (5-methyl- 2H-pyrazol-3-yl)~amine (III-38) : mp 234-235°C; 1H NMR (DMSO) ? 2.35 (3H, s), 6.73 (1H, s) , 7.35 (1H, m) , 7.56 (1H, m) , 7.85 (3H, m), 8.47 (1H, m) , 8.65 (1H, m) , 8.86 (1H, s), 10.49 (1H, s), 12.28 (1H, br s) ; IR (solid) 1560, 1541, 1469, 1360; MS 428.1 (M+H)+. Example 267 [2- (4-Ethylsulfanylphenyl) -guinazolin-4-yl] - (5-methyl-2ff-pyrazol-3-yl)-amine (III-39) : mp 229-231°C; XH NMR (DMSO) 8 1.29 (3H, t), 2.35 (3H, s) , 3.07 (2H, q), 6.76 (1H, S), 7.43 (2H, d) , 7.51 (1H, m), 7.81 (2H, m), 8.41 (2H, d), 8.64 (1H, d) , 10.38 (1H, s), 12.24 (1H, br s) ; IR (solid) 1587, 1574, 1555, 1531, 1484, 1412, 1369; MS 362.1 (M+H)+. Example 268 (5-Cyelopropyl-2H-pyrazol-3-yl) - (2-phenyl- quinazolin-4-yl) -amine (III-40) : mp 218-219°C; 1H NMR (DMS0-d6) ? 0.70-0.80(2H, m) , 0.90-1.00 (2H, m), 6.70 (1H, s), 7.45-7.55 (4H, m) , 7.80-7.85 (2H, m) , 8.45-8.55 (2H, m), 8.65 (1H, d), 10.40 (1H, s), 12.27 (1H, s); IR (solid) 1624, 1605, 1591, 1572, 1561, 1533, 1479, 1439, 1419, 1361, 1327, 997, 828, 803, 780, 762, 710; MS 328.2 (M+H) . Example 269 [2- (4-tert-Butylphenyl) -guinazolin-4-yl] - (5- methyl-2H-pyrazol-3-yl) -amine (III-41) : mp >300°C; 1H NMR (DMS0-d6) ? 1.35 (9H, s) , 2.34 (3H, s), 6.79 (1H, s) , 7.55 (3H, d) , 7.85 (2H, d), 8.39 (2H, d), 8.62 (1H, d) , 10.35 (1H, s), 12.22 (1H, s); IR (solid) 1603, 1599,. 1577, 1561, 1535, 1481, 1409, 1371, 1359, 998, 841, 825, 766, 757; MS 358.3 (M+H)+. gxample 270 [2- (4-Chloropbenyl) -quinazolin-4-yl] - (5- cyclopropyl-2H-pyrazol-3-yl)-amine (III-42) .; ^ NMR (DMSO- d6) 8 0.77 (4H, br m) ,2.05 (1H, m), 6.59 (1H, s), 7.60 (1H, d), 7.85 (2H, d), 7.91 (2H, d), 8.22 (2H, d), 8.65 (1H, S), 10.51 (1H,S), 12.33 (1H,S); MS 362.1 (M+H)+. Example 271 (2-Benzo[l,3Jdioxol-5-yl-quinazolin-4-yl) - (5- methyl-2H-pyrazol-3-yl)-amine (III-43) : XH NMR (DMSO) 8 2.33 (3H, s), 6.13 (2H, s) , 6.78 (lH,s), 7.II (1H, d), 7.80 (1H, t), 7.94 (1H, s) , 8.09 (3H, m), 8.25 (1H, d), 10.34 (1H, s) , 12.21 (1H, s) ; MS 346.5 (M+H)+. foeample 272 [2- (4-Dimethylaminopnenyl) -quinazolin-4-yl] - (5-methyl-2ff-pyrazol-3-yl) -amine (IXI-44) : aH NMR (DMSO- d6) 8 2.02 (6H, s), 2.39 (3H, s), 6.83 (1H, s), 7.71 (1H, d), 7.98 (2H, s), 8,04 (2H, d), 8.33 (2H, d), 8.67 (1H, S), II.82 (1H, s), 12.72 (1H, s); MS 345.3 (M+H)+. Example 273 [2- (3-Methoxyphenyl) -guinazolin-4-yl] - (5- methyl-2JJ-pyrazol-3-yl)-amine (III-45) : mp 226°C; JH MR (DMSO) 8 2.34 (3H,S), 3.92 (3H, s), 6.72 (1H, s), 7.21 (1H, d), 7.57 (1H, t) , 7.79 (1H, t), 8.02 (3H, m), 8.14 (1H, s), 8.79 (1H, d), 10.39 (lH,s), 12.22 (1H, s) ; IR (solid) 1599, 1572, 1538, 1478, 1427, 1359, 833, 761, 661; MS 332.2 (M+H) + . Example 275 (5-CyclQpropyl-2ff-pyrazol-3-yl)-[2-(3,4- dichlorophenyl)-quinazolin-4-yl]-amine (lil-46): ^H NMR (DMSO-d6) 8 0.86 (2H, d) , 1.02 (2H, d), 1.69 (1H, m), 6.56 (1H, s), 7.57 (1H, d), 7.84 (4H, m) , 8.40 (1H, d) , 8.58 (1H, s), 8.64 (1H, s) , 10.53 (1H, s), 12.36 (1H, s) ; MS 396.0 (M+H)+. Example 276 (2-Bipnenyl-4-yl-quinazolin-4-yl) - (5-methyl- 2fl--pyrazol-3-yl)-aiuine (III-47) : .To a mixture of 12-(4- bromo-phenyl) -quinazolin-4-yl] - (5-methyl-2H-pyrazol-3- yl)-amine (IIX-34) (196 mg, 0.51 mmol) and phenylboronic acid (75 mg, 0.62 mmol) in THF:water (1:1, 4 mL) vra.s added Na2CO3 (219 mg, 2.06 mmol), triphenylphosphine (9mg, 1/15 mol%) and palladium acetate (1 mg, 1:135 mol%). The resulting mixture was neated at 80°C overnight, the solvents were evaporated and the residue purified by flash chromatography (gradient of dichloromethane:MeOH) to afford III-21 as a yellow solid {99 mg, 51%): aH NMR (DMSO) 8 2.37 (3H, s), 6.82 (1H, s), 7.39-7.57 (4H, m), 7.73-7.87 (6H, m), 8.57 (2H, d), 8.67 (1H, d), 10.42 (1H, s), 12.27 (1H, s); MS 378.2 (M+H)+. Example 277 [2- (4-Ethyaylphenyl) -quinazolin-4-yi] - (5- methyl-2ff-pyrazol-3-yl)-aniine (III-48) : To a mixture of [2- (4-bromo-phenyl) -quinazolin-4-yl] - (5-methyl-2ff- pyrazol-3-yl)-amiae (III-34) (II4 mg, 0.3 mrnol) , and trimethylsilylacetylene (147 mg, 1.5 mmol)in DMF (2 mL) was added Cul (1.1 mg, 1:50 mol%) , Pd(PPh.3)2Cl2 (4.2 mg, 1:50 mol%) and triethylamine (121 mg, 0.36 mmol) . The resulting mixture was heated at 120°C overnight and the solvent evaporated. The residue was triturated in ethyl acetate and the resulting precipitate collected by filtration. The collected solid was suspended in THF (3 mL) and TBAF (1M in THF, l.leq) was added. The reaction mixture was stirred at room temperature for 2 hours and the solvent evaporated. The residue was purified by flash chromatography (silica gel, gradient of DCM:MeOH) to afford III-48 as a white solid (68 mg, 70%): XH NMR .(DMSO) 6 2.34 (3H, s) , 4.36 (1H, s) , 6.74 (1H, s) , 7.55 (1H, m) , 7.65 (2H, d) , 7.84 (2H, m) , 8.47 (2H,. d) , 8.65 (1H, d), 10.43 (1H, s), 12.24 (1H, s) ; MS 326.1 (M+H)+. Example 278 [2- (3-Ethynylphenyl) - quinazolin-4-yl] - (5- methyl-2ff-pyrazol-3-yl)-amine {XII-49) : mp 204-207°C; H NMR (DMSO) 8 2.34 (3H, s) , 4.28 (1H, s) , 6.74 (1H, s) , 7.55-7.63 (3H, m), 7.83-7.87 (2H, m) , 8.49 (1H, d) , 8.57 (1H, S), 8.65 (1H, d), 10.46 (1H, s), 12.27 (1H, s) ; IR' (solid).1598, 1574, 1541, 1489, 1474, 1422, 1365; MS 326.1 (M+H)+. Example 279 [2- (3-Methylphenyl) -guiaazolin-4-yl] - (5- methyl-2B'-pyrazol-3-yl) -amine (III-50) : A suspension of lH-quinazoline-2,4-dione (10.0 g, 61.7 mmol) in POC13 (60 mL, 644 mmol) and N,N-dimethylani.line (8mL, 63^1 nrniol) was heated under reflux for 2 h. The excess POCl3 was . 300 removed in vacuo, the residue poured into ice, and the resulting precipitate collected by filtration. The crude solid product 2,4-dichloro-quinazoline {6.5 g, 53% yield) was washed with water and dried under vacuum for next step use without further purification. To a solution of the 2,4-dichloro-quinazqline (3.3 g, 16.6 mmol) in anhydrous ethanol (150 mL) was added 5 -methyl-l.ff-pyrazol- 3-yl amine (3.2 g, 32.9 mmol) and the resulting mixture was stirred at room temperature for 4 hours. The resulting precipitate was collected by filtration, washed with ethanol, and dried under vacuum to afford 4.0 g (93% yield) of (2-chloro-quinazolin-4-yl) - (5-methyl-lJ?- pyrazol-3-yl) -amine which was used in the next step without further purification. To a solution of the (2- chloro-quinazolin-4-yl) - (5-methyl-l.ff-pyrazol-3-yl) -amine (50 mg, 0.19 mmol) in DMF (1.0 mL) was added m-tolyl boronic acid (0.38 mmol), 2M Na2CO3 (0.96 mmol) , and tri- t-butylphosphine (0.19 mmol). The flask was flushed with nitrogen and the catalyst. PdCl2(dppf) (0.0II mmol) added in one portion. The reaction mixture was then heated at 80°C for 10 hours, cooled to room temperature, and poured into water (2 mL) . The resulting precipitate was collected by filtration, washed with water, and purified by HPLC to afford III-50 as a pale yellow solid (61mg, 75%): XH NMR (500 MHz, DMSO-d6) 812.3 (br s, 1H) , 10.4 (br s, 1H), 8.75 (d, 1H), 8.30 (s, 1H), 8.25 (d, 1H) , 7.78 (s, 2H), 7.55 (m, 1H), 7.45 (m, 1H) , 7.35 (m, 1H), 6.80 (s, 1H), 2.47 (s, 3H), 2.30 (s, 3H) ; MS 316.1.(M+H). Example 280 [2- (3, 5-Difluorophenyl) -quinazolin-4-yl] - (5- methyl-2H-pyrazol-3-yl) -amine (III-51): 1H NMR (500 MHz, DMSO-dS) ?12.3 (br s, 1H) , 10.8. (br s, 1H) , 8.63 (d, 1H) , 7.95 (d, 2H), 7.85 (m, 2H) , 7.58 (t, 1H) , 7.41 (t, 1H) , 6.59 (s, 1H) , 2.27 (s, 3H) ; MS 338.1 (M+H) . Example 281 [2- (3-Chloro-4-fluorophenyl) -quinazolin-4- yl]-(5-methyl-2H-pyrazol-3-yl)-amine (III-52) : 2H NMR (500 MHz, DMSO-d6) ?12.4 (br s, 1H) , 10.8 (br s, 1H) , 8.65 (d, 1H), 8.50 (d, 1H) , 8.36 (m, 1H), 7.85 (m, 1H) , 7.60 (m, 1H), 6.62 (s, 1H), 2.30 (s, 3H) ; MS 354.1 (M+H). Example 282 (5-Methyl-2H-pyrazol-3-yl) - [2- (3- trifluoromethylphenyl) -guinazolin-4-yl] -amine (III-53) : 1H NMR (500 MHz, DMSO-d6) 812.2 (br, 1H) , 10.45 (br, 1H) , 7.53 (s, 1H) , 7.43 (d, J = 7.2 Hz, 1H) , 7.06 (d, J = 8.2 Hz, 1H) , 6.65 (d, J = 8.3 Hz, 1H), 6.57 (t, J = 7.6 Hz, 1H) , 6.51 (d, J = 7.8 Hz, 1H), 6.43 (t, J = 7.8 Hz, 1H), 6.32 (t, J = 7.6 Hz, 1H), 5.51 (s, 1H) , 2.03 (s, 3H); MS 370.2 (M+H) . Example 283 [2- (3-Cyanophenyl) -guinazolin-4-yl] - (5- methyl-2£r-pyrazol-3-yl)-amine (III-54) : XH NMR (500 MHz, DMSO-d6) 59.01 (s, 1H) , 8.96 (m, 2H) , 8.28 (d, J= 7.3 HZ, 1H), 8.16 (S, br, 2H), 8.06 (t, J = 7.8 Hz, 1H), 7.88 (m, IB), 6.96 (S, 1H), 2.58 (s, 3H); MS 327.1 (M+H). Example 284 [2- (3-Isopropylph.enyl) -quinazolin-4-yl] - (5- methyl-2ff-pyrazol-3-yl) -amine (III-55) : hi NMR (500 MHz, DMSO-d6) 8 8.89 (d, J = 7.5 Hz, 1H) , 8.37 (s, 1H)', 8.26 (s, 1H) , 8.08 (m, 2H) , 7.81 (t, br, 1H) , 7.67 (m, 2H) , 6.88 (s, 1H), 3.12 (m, 1H), 2.40 (s, 3H), 1.38 (d, J = 6.9 Hz, 6H) ; MS 344.2 (M+H). Example 285 (5-Methyl-2H-pyrazol-3-yl) - (2-pyridin-3-yl- guinazolin-4-yl)-amine (III-56) : TH NMR (500 MHz, DMSO-d6) 89.50 (s, 1H) , 8.84 (d, J = 7.3 Hz, 1H) , 8.80 (d, J = 4.4 Hz, 1H) , 8.66 (d, J = 8.2 Hz, 1H) , 7.87 (m, 2H) , 7.77 (tn, 1H), 7.60 (t, J =7.2 Hz, 1H) , 6.67 (s, 1H) , 2.28 (s, 3H) ; MS 303.1 (M+H) . Example 286 [2- (3-Acetylphenyl) -quinazolin-4-yl] - (5- HLethyl-2H-pyrazol-3-yl)-amine (III-57): XH NMR (500 MHz, DMSO-d6) 5 8.80 (s, 1H) , 8.55 (d, J = 7.7 Hz, 1H), 8.42 (d, J = 7.6 Hz, 1H), 8.00 (d, J = 7.0 Hz, 1H), 7.76 (m, 2H) , 7.58 (t, J = 7.7 Hz, 1H), 7.48 (s, br, 1H), 6.60 (s, 1H), 2.49 (s, 3H) , 2.03 (s, 3H) ,- MS 344.1 (M+H). Example 287 12- (3,5-Ditrifluoromethylphenyl) -quinazolin- 4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (III-58) : lH NMR (500 MHz, DMSO-d6) 610.7 (s, br, 1H) , 8.95 (s, 2H) , .8.63 (d, J = 8.2 Hz, 1H), 8.25 (s, 1H) , 7.86 (m, 2H), 7.58 (t, J = 6.9 Hz, 1H), 6.62 (s, 1H), 2.26 (s, 3H) ; MS 438.1 (M+H) . Example 288 [2- (3-Hydroxymethylphenyl) -guinazolin-4-yl] - {5 -methyl - 2JI-pyrazol- 3 -yl) - amine (III-59) : :H MMR (500 MHz, DMSO-d6) S 8.74 (d, J = 7.9 Hz, 1H) , 8.33 (s, 1H) , 8.17 (s, br, 1H), 7.95 (s, br, 1H) , 7.89 (s, br, 1H), 7.62 (m, 3H), 6.72 (s, 1H) , 5.53 (s, 1H), 4.60 (s, 2H) , 2.28 (s, 3H); MS 332.1 (M+H). Example 289 (5-Methyl-2Hr-pyrazol-3-yl) - [2-(3- phenoxyphenyl) -quinazolin-4-yl] -amine (III-60) : mp 231- 232°C; XH NMR (DMSO-d6) 8 2.21 (3H, s) , 6.59 (1H, s) , 7.10-7.22 (4H, m), 7.41-7.45 (2H, m) , 7.54-7.59 (2H, m), 7.81 (2H, S), 8.09 (1H, s), 8.27 (1H, m) , 8.64 (1H, m), 10.40 (1H, s)', 12.20 (1H, s) ; IR (solid); IR (solid) 1589, 1560, 1541, 1536, 1484, 1360, 1227; MS 394.7 (M+H)+. Example 290 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (3- pheaoayphenyl)-quiaazolia-4-yl]-amiae (III-61) : mp 193- 195°C; XH NMR (DMSO-d6) 5 0.67 (2H, m) , 0.93 (2H, m),1.87 (lH,m), 6.56 (1H, s), 7.06-7.20 (4H, m), 7.40-7.43 (2H, m), 7.55-7.59 (2H, m) , 7.81 (2H, s) , 8.II (1H, s), 8.27 . (1H, m), 8.63 (OH, m) , 10.43 (1H, s) , 12.26 (1H, s); IR (solid); IR (solid) 1589, 1574, 1527, 1483, 1369, 1226; MS 420.7 (M+H)+. Example 291 (5-Metayl-2S-pyrazol-3-yl) - (2-taiophen-3-yl- guinarolin-4-yl)-amine (III-62): aH NMR (500 MHz, DMSO-d6) 8II.78 (s, br, 1H), 8.75 (d, J = 8.1 Hz, 1H), 8.68 (s, 1H), 7.98 (dd, J = 7.9, 7.5 Hz, 1H) , 7.89 (m, 2H),.7.81 (m, 1H) , 7.68 (t, J = 7.5 Hz, 1H), 6.69 (s, 1H) , 2.30 (s, 3H); MS 308.1 (M+H). Example 292 (2-Phenyl-quinazolin-4-yl) - (2fl'-pyrazol-3-yi) - amine (III-63): mp 247-249°C; XH NMR (DMSO) 8 6.99 (1H, br s), 7.49-7.58 (5H, m) , 7.81 (1H, brs), 7.83 (2H, m) , 8.47-8.49 (2H, m) , 8.66 (1H, d), 10.54 (1H, s), 12.59 (1H, S) ; IR (solid) 3145, 2922, 1622, 1597; MS 288.2 (M+H) + . Example 293 (2H-Pyrazol-3-yl) - (2-pyridin-4-yl-quinazblin- 4-yl)-amine (XII-64):.mp 285-286°C; ^ NMR (DMSO) 8 6.99 (1H, brs), 7.65 (1H, m), 7.81-7.94 (3H, m) , 8.3-8.35 (2H, m), 8.73 (1H, d) , 8.84-8.90 (2H, m) , 10.76 (1H, s), 12.6 (1H, s); IR (solid) 3180, 2972, 1600, 1574; MS 289.2 (M+H)pxample 294 ,5-Ethyl-2H-pyrazol-3-yl) - (2-paenyl- quiaazolia-4-yl)-amine (III-65): mp 221-222°C; H NMR (DMSO) 5 1.31 (3H, t) , 2.-68 (2H, d) , 6.80 (1H, s) , 7.50- 7.60 (4H, m), 8.45-8.55 (2H, m), 8.65-8.75 (1H, m), 10.44 (lH,s), 12.27 (lH,s); IR (solid) 3190, 1622, 1595, 1575, 1533, 1482, 1441, 1420, 1403, 1361, 758, 7II; MS 316.2 (M+H)+. Example 295 (2-Phenyl-quinazolin-4-yl) - (5-propyl-2H- pyrazol-3-yl)-amine (III-66) : mp 204-205°C; 1H NMR (DMSO- d6) 8 1.02 (3H, t), 1.66-1.75 (2H, m), 2.69 (2H, t), 6.80 (1H, s), 7.45-7.60 (4H,m), 7.80-7.88 (2H, m), 8.45-8.50 (2H, m), 8.65 (1H, d) , 10.39 (1H, s) , 12.25 (1H, s) ; IR (solid) 1621, 1560, 1572, 1533, 1479, 1441, 1421, 1363, 1328, 999, 827, 808, 763, 709, 697; MS 330.2 (M+H)+. Example 296 (5-Isopropyl-2ff-pyrazol-3-yl) - (2-phenyl- quinazolin-4-yl)-amine (III-67) : mp 218-219°C; XH NMR (DMSO-d6) 8 1.36 (6H, d) , 3.05 (1H, m) , 6.86 (1H, s), 7.48-7.59 (4H, m), 7.80-7.88 (2H, m) , 8.49-8.58 (2H, m) , 8.66 (1H, d), 10.47 (1H, s), 12.30 (1H, s); IR (solid) 3173, 2968, 1619, 1593, 1573, 1533, 1478, 1438, 1413, 1398, 1363, 1329, 995, 822, 798, 761, 707, 666, 659; MS 330.2 (M+H)+. Example 297 (5-tert-Butyl-2ff-pyrazol-3-yl) - (2-phenyl- guinazolin-4-yl) -amine (III-68) : mp 136-137°C; XH NMR (DMSO-d6) 8 1.38 (9H, s), 6.87 (1H, br s), 7.51-7.57 (4H, m) , 7.84-7.85 (2H, m) , 8.49-8.51 (2H, tn) , 8.65 (1H, d) , 10.43 (1H, S), 12.21 (1H, br s); IR (solid) 3162, 2963, 1621, 1590, 1572; MS 344.2(M+H)+. Example 298 (5-tert-Butyl-2H-pyrazol-3-yl) - (2-pyridin-4- yl-quinazolin-4-yl) -amine (III-69) : mp >300°C; 1H NMR (DMSO) ? 1.38 (9H, s) , 6.82 (1H, brs), 7.63 (1H, m), 7.86-7.91 (2H, m), 8.32-8.33 (2H, d), 8.69 (1H, d), 8.75-8.76 (2H, d) , 10.60 (1H, s), 12.31 (1H, br s); IR (solid) 3683, 3149, 2963, 1621; MS 345.2(M+H)+. Example 299 (5-Cyclopentyl-2ir-pyrazol-3-yl) - (2-phenyl- qiiinazolin-4-yl)-amine (III-70): mp 240-241°C; ^ NMR (DMSO-d6) 8 1.68-1.89 (6H, m), 2.03-2.17 (2H, m), 3.14- 3.22 [1H, m) , 6.80 (1H, s) , 7.50-7.60 (4H, m), 7.80-7.89 (2H, n) , 8.45-8.52 (2H, m) , 8.67 (1H, d) , 10.52 (1H, s) , 12.26 (1H, s); IR (solid) 2957, 1621, 1591, 1571, 1531, 1476, 1438, 1405, 1370, 1325, 999, 951, 801, 775, 761, 747, 710695, 668, 654; MS 356.2(M+H)+. Example 300 (5-Phenyl-2H-pyrazol-3-yl) - (2-plxenyl- quinazolin-4-yl)-amine (III-71) : mp 207-209°C; aH NMR (DMSO) 5 7.38-7.40 (1H, m), 7.50-7.58 (6H, m), 7.82-7.88 (4H, m) , 8.51 (2H, m) , 8.67 (1H, s), 10.58 (1H, s), 13.II (1H, br s) ; IR (solid) 3345, 3108, 1627, 1612; MS 364.2 (M+H)Example 301 (5 - Carboxy- 2ff-pyrazol - 3 -yl) - (2 -plxenyl - guinazolin-4-yl)-amine (III-72) : (5-Methoxycarbonyl-2.ff- pyrazol-3-yl) - (2-phenyl-quinazolin-4-yl) -amine .(IIX-73) (345mg, 1 mmole in THF, 6 mL) was treated witb NaOH (1M, 4.0 mL), stirred at 50°C for 5 hours, cooled to room temperature, and neutralised with. 1M HC1. The mixture was concentrated in vacuo to remove THF then diluted witb water and the resulting precipitate filtered. The .residual solid was dried at 80°C under vacuum to afford III-72 as an off-white solid (312 mg, 94%) : mp 289-.291°C (dec); ^-H NMR (DMSO) 5 7.45 (1H, br s) , 7.50-7.60 (5H, m), 7.80-7.88 (2H, m) , 7.40-7.50 (2H, m), 8.60-8.70 (1H, d), 10.70 (1H, s) , 13.00-13.80 (2H, br s); IR (solid) 16.99, 1624, 1607, 1570,1539, 1506, 1486, 1398, 1333, 1256, II77, 1004, 827, 764, 705; MS 332.3 (M+H)+. Example 3 02 (5-Methnxycarbonyl-2H-pyrazol-3-yl) - (2- phenyl-quinazolin-4-yl) -amine (III-73) : rap 271-273 °C; 1H NMR (DMSO)6 3.95 (3H, s) , 7.50-7.65 (5H, m) , 7.80-7.98 (2H, m) , 8.40-8.50 (2H, m) , 8.65-8.73 (1H, m) , 10.80 (1H, S) , 13.80 (1H, S); IR (solid) 3359, 1720, 1624, 1597, 1561, 1538, 1500, 1475, 1435, 1410, 1358, 1329, 1283, 1261, II46, II25, 1018, 1010, 944, 827, 806, 780, 763, 703, 690, 670; MS 346.3 (M+H)+. Example 3 03 (5-Bydraxymethyl-2ff-pyrazol-3-yl) - (2-phenyl- quinazolin-4-yl)-arnine (III-74) : A solution of (5- Methoxycarbonyl-2ff-pyrazol-3-yl) - (2-phenyl-quinazolin-4- yl)-amine (III-73) {345mg, limnol) in anhydrous THF (10mL) was treated with lithium borohydride (125mg, 5.75 mmol) at 65°C for 5 hours. The mixture was cooled to room temperature then combined with 2M HC1 and ethyl acetate. Solid sodium hydrogen carbonate was added to achieve pH 8 and the resulting mixture extracted with ethyl acetate. The extracts were dried over magnesium sulphate and concentrated. Purification by flash chromatography (SiO2, methanol-dichloromethane gradient) afforded IXI-74 (95 mg, 30%) as an off-white solid: mp 238-239°C; TH NMR (DMSO) 5 4.58 (2H, d, CH2) , 5.35 (1H, s, OH), 6.94 (1H, s), 7.50-7.60 (4H, m) , 7.85-7.90 (2H, m) , 8.48-8.54 (2H, m) , 8.69 (1H, 1H), 10.40 (1H, s) , 12.48 (1H, s); IR (solid) 1652, 1621, 1603, 1575, 1558, 1539, 1532, 1480, 1373, 1320, 1276, II75, 1057., 1037, 1007, 951, 865, 843, 793, 780, 7124; MS 318.2(M+H)+. Example 304 (5-Methoxymetbyl-2H-pyrazol-3-yl) - (2-phenyl- quinazolin-4-yl) -amine (IIX-75): rap i90-191°C; aH NMR (DMSO) 8 3.34 (3H, s) , 4.45 (2H, s) , 7.00 (1H, s) , 7.50- 7.62 (4H, m) , 7.82-7.90 (2H, m), 8.45-8.52 (2H, m) , 8.65 (1H, br s) , 10.50 (1H, s) , 12.30 (1H, s) ; IR (solid) 3177, 1606, 1589, 1530, 1479, 1441, 1406, 1374, 1363, 1329, II52, 1099, 999, 954, 834, 813, 766,. 707, 691; MS 332.3(M+H)+. Example 305 [5- (3-Hydroxyprop-l-yl) -2H-pyrazol-3-yl] - (2- phenyl-quinazolin-4-yl) -amine (III-76) : A solution of (5- benzyloxypropyl-2.H-pyrazol-3-yl) - (2-phenyl-quinazolin-4- yl)-amine (III-78) (200mg, 0.46nmol) in toluene (4mL) and acetonitrile (8mL) was stirred with trimethylsilyl iodide (0.64ml, 4.6mmol) at 55°C for 3 hours to afford an amber coloured solution. This mixture was diluted with ethyl acetate and aqueous sodium hydrogen carbonate.. The resulting layers were separated, the organic layer was dried over magnesium sulphate and concentrated In vacuo. Purification by flash chromatography (SiOa, methanol- dichloromethane gradient) affords a yellow oil (II5mg). Trituration with dichlorome.thane affords XII-76 as an off-white solid dried at 75°C under vacuum (83mg, 52%): mp 164-165°C; aH NMR (DMSO) 8 1.80-1.90 (2H, m), 2.70-2.80 (2H, m) , 3.50-3.60 (2H, m), 4.59 (1H, s) , 6.80 (1H, sj, 7.50-7.60 (4H, m), 7.82-7.90 (2H, m) , 8.48-8.53 (2H, m) , 8.63 (1H, S), 10.40 (1H, s) , 12.25 (1H, s) ; IR (solid) 1622, 1587, 1574, 1562, 1528, 1480, 1440, 1421, 136B, 1329, II73, 1052, 1030, 1006, 952, 833, 762, 734, 706, 690, 671, 665; MS 346.0(M+H)+: Example 3 06 [5- (3-Methoxyprop-l-yl) -2H-pyrazol-3-yl] - (2- phenyl-quinazolin-4-yl)-amine (III-77) : mp 169-170°C; '"H NMR (DMS0-d6) 5 1.86-1.97 (2H, m) , 2.75 (2H, t) , 3.30 (3H, S) , 3.45 (2H, t) , 6.80 (1H, s) , 7.50-7.60 (4H, m), 7J3O- 7.90 (2H, m), 8.45-8.55 (2H, m), 8.67 (1H, d), 10.30 (1H, S), 12.25 (1H, s); IR (solid) 1620, 1591, 1572, 1532, 1476, 1425, 1408, 1373, 1326, III7, 1003, 831, 764, 714, 695; MS 360.3(M+H)+. Example 307 [5- (3-Benzyloxyprop-l-yl) -2fi'-pyrazol-3-yl] - (2-phenyl-quinazolin-r4-yl)-amine (III-78) : mp 177-178°C; XH NMR (DMSO) 5 1.92-2.03 (2H, m) , 3.76-3.85 (2H, m) , 3.52-3.62 . (2H, m), 4.51 (2H, sj, 6.82 (1H, s), 7.28-7.40 (5H, m), 7.46-7.58 (4H, m) , 7.80-7.85 (2H, m), 8.47-8.52 (2H, m) , 8.66 (1H, d) , 10.45 (1H', s) ; IR (solid) 1621, 1591, 1562, 1532, 1479, 1454, 1426, 1408, 1374, II01, 1006, 835, 766, 738, 712, 696; MS 436.3(M+H)+. Example 308 [5- (3-Aminoprop-l-yl) -2H-pyrazol-3-yl] - (2- phenyl-quinazolin-4-yl) -amine (III-79) : A solution of [5- (3-tert-butoxycarbonylaminoprop-l-yl) -2H-pyrazol-3-yl] - (2-phenyl-quinazolin-4-yl)-amine (III-80) (250mg, 0.56iranol), in dichloromethane (3mL) at 0°C was treated with TFA (2tnL) . The mixture was warmed to room temperature then concentrated in vacuo. The residue was triturated and concentrated from dichloromethane (3x5mL) and ether, then triturated with dichloromethane to crystallize the TFA salt. The resulting solid was collected by filtration and dissolved in a mixture of ethanol (3mL) and water (3mL) . ? Potassium carbonate was added in portions to achieve pH 8 then the mixture allowed to crystallize. The product was collected by filtration and dried at 80°C under vacuum to afford III-79 as an off-white powder (122mg, 63%) : mp 205-207°C; ^ NMR (DMSO) 6 1.68-1.83 (2H, m) , 2.65-2.80( 4H, m) , 6.80 (1H, s) , 7.50-7.60 (4H, m) , 7.80-7.90 (2H, m) , 8.45-8.53 (2H,. m) , 8.65 (1H, d) , 10.45 (1H, br s); IR (solid) 1621, 1598, 1568, 1533, 1484, 1414, 1364, 1327, II69, 1030, 951, 830, 776, 764, 705, 677; MS 345.3(M+H)+. Example 3 09 [5- (3-tert-Butoxyearbonylaminoprop-l-yl) -2H- pyrazol-3-yl] - (2-phenyl-quinazolin-4-yl) -amine (III-80) : mp 199-200°C; XH NMR (DMSO) 5 1.37 (9H, s) , 1.71-1.82 (2H,m), 2.67 (2H, t) , 3.00-3.II (2H, m)., 7.81 (1H, s) , 7.-99 (1H, s) , 7.50-7.60 (4H, m) , 7.80-7.85 (2H, m) , 8.48- 8.52 (2H, m), 8.63 (1H, d), 10.40 (1H, s), 12.26 (1H, m); IR (solid) 2953, 1687, 1622, 1594, 1573, 1535, 1481, 1441, 1419, 1364, 1327, 1281, 1252, II66, 1070, 1028, 998, 951, 848, 807, 768, 740, 728, 710,693; MS 445.3 (M+H) + . Example 310 5-Isopropylcarbamoyl-2ff-pyrazol-3-yl) - (2- phenyl-quinazolin-4-yl) -amine (III-81) : H NMR (500MHz, DMS0-d6) 8 1.20 (d, J - 6.6 Hz, 6H) , 4.13 (m, 1H), 7.42 (br. s, 1H), 7.61 (dd, J.= 7.0, 7.7 Hz, 2H), 7.66 (t, J = 7.1 Hz,. 1H), 7.71 (m, 1H), 7.99 (m, 2H) , 8.39 (m, 1H), 8.42 (d, J = 7.1 Hz, 2H), 8.74 (d, J = 8.2 Hz, 1H), II.41 (br. S, 1H) ; EI-MS 373.2 (M+H) ; HPLC-Method C, Rt 14.09 min. Example 3II {5-Allyicarbamoyl-2ff-pyrazol-3-yl) - (2-pnenyl- quinazolin-4-yl)-amine (III-82): ^ NMR (500MHz, DMSO-d6) 8 4.02 (m, 2H) , 5.15 (m, 1H) , 5.23 (m, 1H) , 5.94 (m, 1H) , 7.45 (br. S, 1H), 7.60 (t, J = 6.9 Hz, 2H), 7.64 (m, 1H), 7.72 (m, 1H), 7.98 (m, 2H), 8.43 (m 2H), 8.72 (d, J = 8.2 Hz, 1H) , 8.84 (br. s, 1H), II.34 (br. s, 1H); EI-MS 371.2 (M+H); HPLC-Method C, Rt 13.67 min. Example 312 [5- (2-Methoxyethylcarbambyl) -2H-pyrazol-3- yl]-(2-phenyl-quinazolia-4-yl)-amine (III-83) : 1H NMR (500MHz, DMSO-d6) 5 3.32 {s, 3H) , 3.48 (m, 4H) , 7.36 (br. s, 1H), 7.62 (m, 2H) , 7.63 (m, 1H) , 7.71 (m, 1H) , 7.98 (m, 2H), 8.41 (dd, J .= 1.4, 7.0, 2H) , 8.70 (m, 2H), II.30 (br. S, 1H) ; EI-MS 389.2 (M+H) ; HPLC-Method C, Rt 12.37' min. Example 313 (5-Benzylcarbainoyl-2H-pyrazol-3-yl) - (2- phenyl-quinazolin-4-yl)-amine (III-84) : H NMR (500MHz, DMS0-d6) 8 4.52 (d, J = 6.0 Hz, 2H), 7.29 (m, 1H), 7.38 (d, J = 4.2 Hz, 4H) , 7.58 (t, J = 7.5 Hz, 2H), 7.63 (m, 1H), 7.72 (m, 1H) , 7.98 (in, 2H) , 8.43 (d, J = 7.7 Hz, 2H), 8.72 (d, J ? 7.5 Hz, 1H), 9.23 (br. s, 2H), II.34 (br. s, 1H) ; EI-MS 421.2 (M+H) ; HPLC-Method C, Rt 16.76 min. Example 314 (S-Cyclohexylcarbamoyl-iff-pyrazol-S-yl) - (2- phenyl-quinazoliii-4-yl)-amine (III-85) : aH MMR (500MHz, DMSO-d6) 5.1.16 (m, 1H), 1.34 (m, 4H) , 1.62 (d, J = 2.6 Hz, 1H) , 1.76 (m, 2H) , 1.85 (m, 2H), 3.79 (m, 1H), 7.43 (m, 1H) , 7.60 (t, J = 7.2 Hz, 2H) , 7.65 (t, J = 7.1 Hz, 1H), 7.71 (ddd, J = 2.2, 5.4, 8.2 Hz, 1H), 7.98 (m, 2H), 8.35 (m, 1H) , 8.43 (dd, J= 1.4, 7.2 Hz, 2H) , 8.72 (d, J = 8.2 Hz, 1H) , II.34 (br. s, 1H) ; EI-MS 413.5 (M+H) ; HPLC-Method C, Rt 17.18 min. Example 315 (5-Dieth.ylcarbamoyl-2H-pyrazol-3-yl) - (2- phenyl-quinazolin-4-yl) -amine (XIX-86) : ^H NMR (500MHz, DMS0-d6) 5 1.18 (br. s, 3H), 1.25 (br. s, 3H), 3.49 (br. S, 2H), 3.69 (b. s, 2H), 7.21 (s, 1H), 7.59 (t, J = 6.9 HZ, 2H), 7.62 (m,'lH), 7.70 (m, 1H), 7.96 (m, 2H), 8.39 (d, J = 7.1 Hz, 2H), 8.74 (d, J = 8.4 Hz, 1H), II.37 (br. s, 1H) ; EI-MS 387.2 (M+H); HPLC-Method C, Rt 14.50 min. Example 316 15- (Benzyl-methyl-carbamoyl) -2H-pyxazol-3- yl] -(2-phenyl-quinazolin-4-yl)-amine (III-87): JH NMR (500MHz, DMSO-d6) 6 3.33 (s, 3H) , 4.75 (s, 2H) , 7.26 (m, 1H), 7.31 (m, 1H), 7.38 (m, 4H), 7.58 (m, 2H), 7.70 (m, 1H), 7.95 (m, 3H), 8.26 (m, 1H), 8140 (d, J = 7.8 Hz, 2H) , 8.75 (m, 1H) , II.2 (br. S, 1H) ; EI-MS 435.2 .(M+H); HPLC-Method C, Rt 16.77 min. Example 317 (2-Phenvl-cruinazolin-4-yl) - (S- propylcarbaaoyl-2ff-pyrazol-3-yl)-amine (III-88) : XH NMR (500MHz, DMS0-d6) S 0.94 (t, J = 7.3 Hz, 3H) , 1.57 (m, 2H)., 3.24 (q, J = 6.5 Hz, 2H) , 7.39 (br. s, 1H) , 7.60 (t, J =7.3 Hz, 2H), 7.64 (m, 1H), 7.71 (br. t, J = 6.5 Hz, 1H), 7.98 (m, 2H), 8.42 (d, J = 7.2 Hz, 2H), 8.61 (br. s, 1H), 8.72 (d, J = 8.5 Hz, 1H), II.34 (br. S, 1H) ; EI-MS 373.3 (M+H); HPLC-Method C, Rt 13.51 min. Example 318 [5- (Ethyl-isopropyl-carbamoyl) -2ff-pyxazol-3- yl] - (2-phenyl-quinazolin-4-yl) -amine (III-89) : ^ NMR (500MHz, DMSO-d6) 8 0.92 (t, J = 7.4 Hz, 6H) , 1.52 (m,. 2H) , 1.59 (m, 1H) ', 3.79 (m, 2H) , 7.53 (br. s, 1H) , 7.57 (t, J = 7.5 Hz, 2H) , 7.65 (t, J = 7.2 Hz, 1H) , 7.71 (m, 1H), 7.99 (m, 2H), 8.23 (br. d, J = 8.8 Hz, 1H), 8.46 (d, J - 7.5 Hz, 2H), 8.74 (d, J = 8.4 Hz, 1H), II.34 (br. s, 1H) ; EI-MS 4.01.2 (M+H); HPLC-Method C, Rt 15.51 min. Example 319 (5-Cyclopropylcarbamoyl-2H-pyrazol-3-yl) - (2- phenyl-quinazolin-4-yl)-amine (III-90) : ^ NMR (500MHz, DMSO-d6) 8 0.60 (m, 2H) , 0.74 (m, 2H), 2.86 (m, 1H), 7.34 (br. s, 1H) , 7.62 (m, 3H), 7.70 (m, 1H), 7.97 (m, 2H), 8.41 (d, J = 7.9 Hz, 2H) , 8.63 (br. s, 1H), 8.72 (d, J = 7.8 Hz, 1H) , II.35. (br. S, 1H) ; EI-MS 371.2 (M+H) ; HPLC- Method C, Rt 12.64 min. Example' 320 (5-Isobutylcarbamoyl-2H-pyxazol-3-yl) - (2- phenyl-quinazolin-4-yl)-amine (III-91) : 1H NMR (500MHz, DMSO-d6) ? 0.94 (d, J = 6.7 Hz, 6H), 1.88 (m, 1H), 3.12 (t, J = 6.4 Hz, 2H), 7.45 (br. S, 1H), 7.58 (t, J = 7.2 Hz, 3H), 7.64 (t, J = 7.1 Hz, 1H) , 7.71 (m, 1H), 7.98 (m, 2H), 8.44 (dd, J = 1.3, 7.9 Hz, 2H), 8.62 (br. s, 1H), 8.72 (d, J = 8.3 Hz, 1H), II.33 (br. s, 1H); EI-MS 387.2 (M+H); HPLC-Method C, Rt 14.70 min. Example 321 {5-[ (3S)-3-Methoxymethyl-pyrrolidine-l- carbonyl] -2ff-pyrazol-3-yl}- (2-pnenyl-quinazoiin-4-yl) - amine (III-93) : XH NMR (500MHz, DMS0-d6) 5 2.00 (m, 2H) , 2.12 (m, 1H), 3.29 (s, 3H), 3.45. (t, J = 8.7 Hz, 1H), 3.57 (dd, J = 3.2, 9.3 Hz, 1H), 3.86 (m, 1H), 3.92 (m, 1H), 4.36 (m, 2H) , 7.45 (br. s, 1H), 7.59 (t, J=7.2 Hz, 2H), 7.63 (m, 1H) , 7.69 (m, 1H),.7.97 (m, 2H), 8.40 (d, J = 7.5 Hz, 2H) , 8.74 (d, J = 7.6 Hz, 1H), II.38 (br. s, 1H) ; EI-MS 429.2 (M+H) ; HPLC-Method C, Rt 13.84 min. Example 322 (2-Phenyl-quinazol±n-4-yl) - (5-jn- tolylcarbamoyl-2ff-pyrazol-3-yl) -amine (III-94) : TH NMR (500MHz, DMS0-d6) 5 2.33 (s, 3H) , 6.97 (d, J = 7.5 Hz, 1H) , 7.27 (t, J = 7.8 Hz, 1H) , 7.62 (m", 7H) , 7.72 (m, 1H) , 7.98 (m, 2H), 8.46 (dd, J = 2.0, 7.9 Hz, 2H), 8.71 (m, 1H) , 10.29 (s, 1H), II.31 (br. S, 1H); EI-MS 421.2 (M+H); HPLC-Method C, Rt 17.II min. Example 323 (2-Phenyl-quinazolin-4-yl) -(5-p- tolylcarbamoyl-2H-pyrazol-3-yl)-amine (III-95): 1H NMR (500MHz, DMSO-d6) 6 2.30 (s, 3H), 7.20 (d, J =8.3 Hz, 2H) , 7.62 (m, 5H), 7.68 (d, J = 8.3 Hz, 2H) , 7.72 (m, 1H) , 7.98 (m, 2H), 8.46 (dd, J = 1.8, 7.0 Hz, 2H), 8.72 (m, 1H), 10.31 (s, 1H), II.36 (br. S, 1H); EI-MS 421.2 (M+H) ; HPLC-MetHod C, Rt 16.95 min. Example 324 (5-Methylcarbamoyl-2H-pyrazol-3-Yl) - (2- phenyl-quinazolin-4-yl) -amine (III-96) : 1H NMR (500MHz, DMSO-d6) 5 2.82 (d, J = 4.6 Hz, 3H) , 7.31 (br. s, 1H) , 7.62 (m, 3H) , 7.69 (m, 1H) , 7.97 (m, 2H) , 8.42 (d, J = 7.1 Hz, 2H), 8.59 (br. s, 1H), 8.71 (d, J = 8.0 Hz, 1H), II.30 (br. s, 1H) ; EI-MS 345.1 (M+H); HPLC-Method C, Rt II.02 min. Example 325 [5- (Morpholine-4-carbonyl) -2ff-pyrazol-3-yl] - {2-phenyl-quinazolin-4-yl)-amine (III-97) : XH MMR (500MHz, DMSO-d6) 5 3.33 (m, 4H) , 3.83 (m 4H) , 7.34 (br. s, 1H) , . 7.53 (m, 4H) , 7.86 (m, 2H), 8.43 (m, 2H) , 8.67 (d, J = 8.6 Hz, 1H), 10.70 (s, 1H) , 13.56 (s, 1H) ; EI-MS 401.2 (M+H) ; HPLC-Method A, Rt 2.68 min. Example 326 [5- (1 -Methylpiperazine-4-carbonyl) -2H- pyrazol-3-yl] - (2-phenyl-quinazolin-4-yl) -amine (III-98) : XH NMR (500MHz, DMSO-d6) 8 2.25 (s, 3H) , 2.43 (m, 4H) , 3.87 (m 4H), 7.33 (br. s, 1H) , 7.53 (m, 4H) , 7.87 (m, 2H) , 8.45 (m, 2H) , 8.67 (d, J. = 7.6 Hz, 1H) , 10.70 (s, 1H) , 13.30 (s, 1H) ; EI-MS 414.2 (M+H); HPLC-Method A, Rt 2.38 min. Example 327 [5- (2-Hydroxyethylcarbamoyl-2fl-pyrazol-3-yl] - (2-phenyl-quiaazolin-4-yl)-amine (III-99) : ^ NMR (500MHz, DMSO-d6) 8 3.36 (m, 2H), 3.52 (m, 2H), 4.79 (m, 1H), 7.50 (m, 5H), 7.83 (m, 2H), 8.50 (m, 4H) , 10.52 (br. s, 1H), 13.25 (s, 1H) ; EI-MS 375.1 (M+H) ; HPLC-Method A, Rt 2.51 min. Example 328 (5-Carbamoyl-2H-pyrazol-3-yl) - (2-phenyl- guinazolin-4-yl) -amine (III-100) : To a solution of 5-(2- phenyl-quinazolin-4-ylamino) -lH-pyrazole-3-carboxylic acid 2,5-dioxo-pyrrolidin-l-yl ester (270 mg, 0.63 mmol) in DMF (20 ml) was added a solution of ammonia in 1,4- dioxane (0.5 M, 10 ml). The resulting mixture was stirred at room temperature for 24 h. After concentration of the solvents, the residue was added to water (20 ml) . The resulting precipitate was collected to afford III-100 (168 mg, 80%)as a yellow solid. 1H NMR (500MHz, DMSO-d6) ? 7.77-7.51 (m, 6H) , 7.86 (br s, 2H) , 8.II (m, 1H) , 8.50 (m, 2H) , 8.63 (m, 1H), 10.52 (s, 1H) , II.25 (s, 1H) ; EI-MS 331.1 (M+H); HPLC-Method A, Rt 2.52' min. Example 329 (4-Bromo-2H-pyrazol-3-yl) -(2-phenyl- quinazolin-4-yl)-amine (III-101) : Prepared according to Method A to afford a yellow solid, mp 189°C; 1H NMR (DMSO- d6) 8 7.44-7.46 (3H, m), 7.58 (1H, m) , 7.87 (2H, d) , 8.15 (1H, s) , 8.31-8.34 (2H, m) , 8.49 (1H, d) , 10.08 (1H, s) , 13.13 (1H, S); IR (solid) 3286, 2969, 1738, 1632; MS 366.2/368.2(M+H)+. Example 330 (4-Bromo-5-methyl-2H-pyrazol-3-yl) - (2-phenyl- quinazolin-4-yl)-amine (III-102): mp 183-185°C; 1H NMR (DMSO) ? 2.33 (3H, br s), 7.44-7.46 (3H, m), 7.57 (1H, m) , 7.84-7.87 (2H, m), 8.31-8.34 (2H, m), 8.48 (1H, d) , 10.05 (1H, s), 12.91 (1H, br s) ; IR (solid) 3362, -3065, 2831, 1619, 1578; MS 380-2/382.2(M+H)+. Example 331 (4-Cyano-2H-pyrazol-3-yl) -(2-phenyl- quiaazolin-4-yl)-amine (III-103) : rap >250°C; 1H NMR (DMSO) ? 7.47-7.49 (3H, m), 7.64 (1H, m), 7.91 (2H, m) , 8.40- 8.43 (2H, m), 8.53 (1H, d), 8.71 (1H, d), 10.61 (1H, s), 13.60 (1H, s); IR (solid) 3277, 3069, 2855, 2231, 1625; MS 313.2(M+H)+. Example 332 (5-Methyl-2H-pyrazol-3-yl) - (2-morpholin-4-yl- quinazolin-4-yl) -amine {III-104): mp 223-224°C; 1H NMR (DMSO) ? 2.26(3H, s), 3.65(4H, m), 3.75(4H, m), 6.44(1H, s) , 7.12(1H, d) , 7.33(1H, d) , 7.56(1H, t) , 8.37(1H, d) , 10.0K1H, s), 12.13(1H, br s) ; IR (solid) 1621, 1578, 1537, 1475, 1434, 1385; MS 3II.0 (M+H)+. • Example 333 (5-Methyl-2H-pyrazol-3-yl) - (2-piperazin-l-yl- quinazolin-4-yl) -amine (III-105): mp 179-181°C; H NMR (DMSO) 5 2.26(3H, s), 2.74 (4H, br s) , 3.71(4H, br s), 6.43(1H, s), 7.08(lH, t), 7.3O(1H, d), 7.53(1H, t), 8.34 (1H, d) , 9.50 (1H, s) , 12.08 (1H, br s) ,- IR (solid) 2853, 1619, 1603, 1566, 1549, 1539; MS 310.0 (M+H)+ Example 334 [2- (4-Methylpiperidin-l-yl) -quin.azolin-4-yl] - (5-methyl-2H-pyrazol-3-yl)-amine (III-106) : mp 148-150°C; ^ NMR (DMSO) 8 1.06(3H, d), 1.03(2H, m), 1.51-1.70(3H, m) , 2.26(3H, s), 2.86(2H, m), 4.73(2H,d), 6.44(1H, s), 7.06(lH, d), 7.29(1H, d), 7.52(1H, t), 8.32(1H, d), 9.92(1H, s), 12.09(lH, br s); IR (solid) 2917, 2840, 1629, 1593, 1562, 1546, 1486; MS 323.0 (M+H)+. Example 335 12- (4-Methylpiperazin-l-yl) -quinazolin-4-yl] - (5-methyl-2H-pyrazol-3-yl)-amine (III-107): mp 105-107°C; 1H NMR (DMSO) ? 2.21(3H, s), 2.26(3H, s), 2.34(4H, m), 3.75(4H, m), 6.45(1H, s), 7.09(lH, t), 7.31(1H, d) , 7.54(1H, t), 8.34(1H, d), 9.96(1H, s), 12.12(1H, br s); IR (solid) 2934, 2844, 2804, 1620, 1593, 1572, 15360, 1476; MS 324.0 (M+H)+. Example 33 6 (5-Methyl-2H-pyrazol-3-yl) - (2-piperidin-l-yl- quinazolin-4-yl)-amine (III-108) : rap 294°C; 1H NMR (DMSO) S 1.45-1.58 (4H, m), 1.63 (2H, m), 2.26 (4H, m) , 6.45 (1H, br s) , 7.06 (1H, t) , 7.29 (1H, d) , 7.52 (1H, t) , 8.33 (1H, d) , 9.92 (1H, s) , 12.II (1H, br s); IR (solid) 2929, 2847, 1632, 1591, 1500, 1482, 1437, 1382; MS 309.3 (M+H)+. Example 337 (2-Azepan-l-yl) -quinazolin-4-yl] - (5-metbyl- 2H-pyrazol-3-yl)-amine (III-109) : mp 269°C; 1H NMR (DMSO) ? 1.50 (4H, br s), 1.76 (4H, br s), 2.25 (3H, s), 3.78 (4H, t) , 6.55 (1H, br s) , 7.03 (1H, t) , 7.28 (1H, d) , 7.50 (1H, t), 8.33 (1H, d), 9.92 (1H, s) , 12.09 (1H, br s); IR (solid) 3427, 2963, 2927, 2909, 2872, 2850, 1623, 1595, 1586, 1568., 1504, I486, 1468, 1386, 1427; MS 323.3 (M+H) + . Example 33 8 [2-(4-(2-Hydroxyethylpiperidin-l-yl)- quinazolin-4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine {XIX- II0): mp 175°C; XH NMR (DMSO) 5 1.08 (2H, m), 1.38 (2H, m) , 1.57-1.83 (3H, m), 2.26 (3H, s), 2.85 (2H, t), 3.47 (2H, m) , 4.38 (1H, t), 4.75 (2H, d) , 6.45 (1H, br s), 7.06 (1H, t), 7.29 (1H, d), 7.52 (1H, t), 8.32 (1H, d), 9.93 (1H, s), 12.12 (1H, br s); IR (solid) 3365, 3073,. 2972, 2868, 1622, 1604, 1586, 1568, 1486, 1463, 1440, 1394; MS 353.2 (M+H) + . Example 339 (5-Cyclopropyl-2H-pyrazol-3-yl)-[2-(4- methylpiperidin-1-yl) -quinazolin-4-yl] -amine (III-lll) : To a solution of (5-cyclopropyl-lH-pyrazol-3-yl) - (2- chloro-quinazolin-4-yl) -amine (II8 ing, 0.41 mmol) in tert-butanol (3.0 mL) was added 4-methylpiperidine (0.49 mL, 4.1 mmol) and the reaction mixture heated at reflux overnight. The reaction mixture was concentrated In vacuo and the residue dissolved in a mixture EtOH: water (1:3,'4 mL) . Potassium carbonate (57mg, 0.41 mmol) was added and the mixture stirred at room temperature for 2 hours. The resulting suspension was filtered, washed with water (x2) / and rinsed with Et2O (x2) to afford III- III as a white solid (123mg, 85%): mp 190°C; XH NMR (DMSO) 5 0.66 (2H, S) , 0.93. (5H, tes), 1.07 (2H, d), 1.66 (3H, s) , 1.91 (1H, s), 2.85 (2H, t) , 4.72 (2H, d) , 6.33 (1H, s) , 7.06 (1H, t), 7.29 (1H, d), 7.52 (1H, t) , 8.31 (1H, d), 9.95 (1H, s), 12.18 (1H, br s); IR (solid) 2925, ' 2852, 1622, 1590, 1581, 1558, 1494, 1481, 1453, 1435, 1394; MS 349.2 (M+H)+. Example 340 [2- (l,4-D±oxa-8-aza-sp±ro [4,5] dec-8-yl) - quinazolin-4-yl]- (5-methyl-2J5r-pyrazol-3-yl) -amine (III- II2): mp 191°C; XH NMR (DMSO) 8 1.65 (4H, S.) , 2.26 (3H, s), 3.90 (4H, s), 3.93 (4H, s) , 6.43 (1H, br s), 7.09 (1H, t) , 7.32 (1H, d) , 7.54 (1H, t) , 8.35 (1H, d.) , 9.99 (1H, br s), 12.13 (1H, br s); IR (solid) 3069, 2964, 2927, 2868, 1618, 1581, 1568, 1540, 1495, 1481, 1435, 1390; MS 367.3 (M+H)+. Example 341 [2- (4-Cyclopentylamino-piperidin-l-yl) - guinazolin-4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (III- II3): mp 191°C; 1H NMR (DMSO) ? 1.33 (2H, d) , 1.65 (4H, s), 1.87 (2H, d), 2.20 (1H, s), 2.26 (3H, s), 2.49 (2H, s), 3.00 (2H, t), 3.36 (2H, s) , 4.61 (2H, d), 6.45 (1H, br s), 7.07 (1H, s), 7.31 (1H, d), 7.52 (1H, s), 8.33 {1H, d) , 9.94 (1H, br s), 12.12 (1H, br s) ; IR (solid) 3371, 2943, 1622, 1600, 1581, 1545, 1509, 1463, 1440, 1390; MS 378.2 (M+H)+. Example 342 12- (4-Hydroxypiperidin-l-yl) -guinazolin-4- yl]-(5-methyl-2jr-pyrazol-3-yl)-amine (III-II4): mp 123°C; XH SMR (DMSO) 8 1.34 (2H, d), 1.80 (2H, d), 2.26 (3H, s) , 3.24 (2H, t), 3.72 (1H, br s), 4.39 (2H, d), 4.70 (1H, d), 6.44 (1H, br s), 7.07 (1H, t), 7.30 (1H, d),7.53 (1H, t), 8.33 (1H, d), 9.94 (1H, br s), 12-II (1H, br s>; IR (solid) 3265, 3151, 2927, 2863, 1622, 1600, 1572, 1540, 1504, 1476, 1440, 1390, 1349, 1066, 1098; MS 325.3 (M+H)+. Example. 343 (5-Cyclopropyl-2i?-pyrazol-3-yl) - [2- (4- hydroxy-4-phenylpiperidia-l-yl) -guinazolin-4-yl] -amine (III-II5) : nrp 131°C; '"H NMR (DMSO) 5 0.64 (2H, q) , 0.93 {2H, q), 1.68 (2H, d), 1.83-1.97 (3H, m) , 3.20-3.45 (2H, m) , 4.69 (2H, d), 5.II (1H, s) , 6.37 (1H, br s), 7.08 (1H, t)', 7.20 (1H, t), 7.31 (3H, t) , 7.49 (2H, d), 7.53 (1H, t), 8.33 (1H, d) , 9.98 (1H, br s), 12-18 (1H, br s); IR (solid) 3362, 2952, 2934, 29II, 2870, 2825, 1618, 1584, 1570, 1559, 1536, 1481, 1459, 1431, 1372, 1336, 1213, 994; MS 427.6. (M+H)+. Exaarple 344 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (1,3- dihydro-isoindol-2-yl)-quinazolin-4-yl]-amine (III-II6) : Prepared according to Method E-I to afford an off-white solid, mp 237°C; hi NMR (DMSO-d6) 5 0.79 (2H, s), 1.00 (2H, d) , 1.99 (1H, m), 4.92 (4H, d), 6.72 (1H, br s), 7.13 (1H, t), 7.33 (2H, s), 7,30-7.48 (3H, m), 7.58 (1H, t) , 8.40 (1H, d) , 10.12 (1H, s), 12.17 (1H, s); IR (solid) 3449, 3318, 2850, 1623, 1595, 1577, 1541, 1509, 1482, 1432, 1391, 1359, II41, 1027, 877, 814; MS 369.4 (M+H)+. Example 345 (2-Azepan-l-yl)-quinazolin-4-yl]-(5- cyclopropyl-2H-pyrazol-3-yl) -amine (III-H7) : mp 199- 200°C; 1H NMR (DMSO-d6) ? 0.60-0.70 (2H, n), 0.90-1.00 (2H, m) , 1.45-1.57 (4H, m) , 1.70-1.85 (4H, m), 1.88-1.97 (1H, m), 3.75-3.87 (4H, m), 6.42 (1H, s), 7.02 (1H, t), 7.27 (1H, d) , 7.49 (1H, t), 8.29 (1H, d) , 9.91 (1H, s) , 12.19 (1H, br s) ; IR (solid) 2929, 1624, 1595, 1581, . 1563, 1542, 1498, 1482, 1440, 1426, 1397, 1356, 1305, 1000, 825, 754; MS 349.2 (M+H)+. Example 346 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (3,4- dihydro-lH-iBoquinolin-2-yl) -quinazolin-4-yl] -amine (III- II8): mp 182-184°C; 1H NMR (DMSO) ? 0.75 (2H, d) , 1.02 (2H, d) , 1.96 (1H, m) , 2.89 (2H, m) , 4.05 (2H, m) , 4.94 (2H, s) , 6.46 (1H, s), 7.10 (1H, t), 7.21 (4H, d) , 7.37 (1H, d) , 7.55 (1H, d) , 8.36 (1H, d), 10.05 (1H, s) , 12.23 (1H, br s) ; IR (solid) 1621, 1581, 1560, 1537, 1479, 1456, 1426, 1396, 1374, 1341, 1222; MS 383.3 (M+H)+. Example 347 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (2,3- dibydro-indol-1-yl)-quinazolin-4-yl]-amine (III-II9) : mp 150-153°C; 1H NMR (DMSO) ? 0.74 (2H, d) , 0.98 (2H, d) , 1.96 {1H, m) , 3.15 (2H, t) , 4.25 (2H, t) , 6.45 (1H, br s) , 6.88 (1H, t), 7.09 (1H, t), 7.20 (2H, m), 7.53 (1H, d) , 7.65 (1H, t), 8.43 (2H, br s), 10.09 (1H, s) , 12.28 (1H, br s) ; IR (solid) 1621, 1588, 1577, 1564, 1537, 1487, 1455, 1425, 1386, 1259; MS 369.3 (M+H)+. Example 348 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2-(4- hydroxymethylpiperidin-1-yl) -guinazolin-4-yl] -amine (III- 120): mp 142°C; 1H MMR (DMSO) ? 0.67 (2H, d) , 0.96 (2H, d) , 1.10 (2H, q) , 1.55-1.70 (3H, m) , 1.91 (1H, m) , 2.85 (2H, t), 3.28 (2H, s), 4.48 (1H, s) , 4.76 (2H, d) , 6.34 (1H, s), 7.06 (1H, t), 7.30 (1H, d) , 7.52 (1H, t), 8.31 (1H, d), 9.96 (1H, s), 12.19 (1H, s); IR (solid) 3363, 3000, 2927, 2854, 1618, 1604, 1573, 1536, 1509, 1477, 1436, 1395, 1354, 1314, 1241, II86, 1091, 995, 941, 823; MS 365.8 (M+H)+. Example 349 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (3,4- dihydro-2H-quinolin-l-yl) -quinazolin-4-yl] -amine (III- 121): mp 137-145°C; 1H NMR (DMSO-d6) ? 0.55 (2H, d) , 0.88 (2H, d), 1.78 (1H, m) , 1.92 (2H, t) , 2.75 (2H, t), 4.04 (2H, t) , 6.20 (1H, br s) , 6.97 (1H, t) , 7.14 (1H, m) , 7.19 (1H, t), 7.42 (1H, d), 7.61 (1H, t), 7.67 (1H, d), 8.43 (1H, d), 10.04 (1H, s), 12.21 (1H, br s); IR (solid) 1622, 1572, 1539, 1493, 1454, 1420, 1373, 1249; MS 383.3 (M+H)+. Example 350 (5-Methoxycarbonyl-2H-pyrazol-3-yl)-[2- (piperidine-1-yl) -quinazolin-4-yl] -amine (III-122) : Tl NMR (500MHz, CDC13) 81.7-1.8(6H, m) , 8 3.8 (4H, m), 8 3.9 (3H, s), 5 5.5 (1H, s), 8 7.15 (1H, t), 8 7.4 (1H, d), 8 7.6 (1H, t) , 8 8.0 (1H, d) . HPLC-Method B, (starting with 95% H20) Rt 7.4 min; MS (ES+) 353.24 (M+H) . Example 351 [5-(Piperidine-1-carbonyl)-2ff-pyrazol-3-yl]- [2- (piperidine-1-yl) -quinazolin-4-yl] -amine (III-123) : HPLC-Method B, (starting with 95% H20:0.1% TFA) Rt 8.0 min; MS (ES+) 406.30, (ES-) 404.30. Example 352 (5-Hydroxymetbyl-2H-pyrazol-3-yl) -[2- (piperidin-1-yl)-quinazolin-4-yl]-amine (III-124): To a solution of III-122 (10.0 mg, 0.028 mmol) in THF (6 mL) at ambient temperature was slowly added a 1M solution of LiAlH4 in THF (0.05 mL, 0.05 mmol). After 15 minutes the solution was quenched with water and IN HCl. The product was extracted from the aqueous layer with EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by preparatory HPLC to afford III-124 (4.0 mg, 44%). HPLC- Method B, (starting with 95% H2O:0.1% TFA) Rt 6.1 min; MS (ES+) 325.13 (M+H), (ES-) 323.13 (M-H). Example 353 (5-Carbamoyl-2H-pyrazol-3-yl) - [2- (piperidin- 1-yl)-quinazolin-4-yl]-amine (III-125) : A solution of III-122 (1.5 g, 4.3 mmol) in 2.0 M NH3/MeOH (100 mL) was heated at II0°C for 2 days. The dark brown reaction mixture was concentrated in vacuo to afford a viscous oil which was purified by column chromatography to yield 0.7 g (50%) of III-125. 1H NMR (500MHz, CD3OD-d3) ?1.6 (4H, m); 81.7 (2H,m), ? 3.3 (1H, s) , ? 3.8 (4H, m) , ? 5.5 (1H, S), ? 7.15 (1H, t), ? 7.45 (1H, d), ? 7.55 (1H, t) , ? 8.0 (1H, d) ; HPLC-Method B, (starting with 95% H2O:0.1% TFA) Rt 5.9 min; MS (ES+) 3.38.13, (ES-) 336.15. Example 354 (5-Carbamoyl-2H'-pyrazol-3-yl) - [2- (4- methylpiperidin-1-yl)-guinazolin-4-yl]-amine (III-126) : HPLC-Method B, (starting with 95% H2O:0.1% TFA) Rt 6.4 min; MS (ES+) 352.19, (ES-) 350.20. Example 355 (5,7-Difluoro-lH-indazol-3-yl) - (2-phenyl- 5,6,7,8-tetrahydroquinazolin-4-yl)-amine (III-127) : XH NMR (500 MHz, DMSO-de) 813.7 (s, 1H), 10.3 (s, br, 1H) , 7.90 (d, 2H), 7.52 (t, 1H) , 7.45 (m, 3H),.7.26 (d, 1H), 2.99 (m, 2H) , 2.75 (m; 2H) , 1.95 (br, 4H) ppm; MS (ES+) 378.24 (M+H); .(ES-) 376.23 (M-H) ; HPLC-Method A, Rt 3.04 min. Example 356 (2-Phenyl-5,6,7,8-tetrahydroquinazolin-4-yl) - (5-trifluoramethyl-lff-indazol-3-yl)-amine (III-128) : lH NMR (500 MHz, DMSO-d6) 813.4 (e, 1H) , 10.2 (s, br, 1H) , 8.13 (s, 1H), 7.86 (d, 2H), 7.78 (d, 1H), 7.69 (d, 1H) , 7.50 (t, 1H), 7.35 (dd, 2H) 7 2.89 (m, 2H) , 2.72 (m, 2H) , 1.90 (s, br, 4H) ppm.; MS (ES+) 410.24 (M+H); (ES-) 408.23 (M-H); HPLC-Method A, Rt 3.19 nin. Example 357 (7 - Fluoro - Iff- indazol - 3 -yl) - (2 -phenyl - quinazolin-4-yl)-amine (III-129) : XH NMR (500 MHz, DMSO- d6) 813.6 (s, 1H) , II.1 (s, br, 1H) , 8.65 (d, 1H) , 8.03 (d, 2H) , 7.95 (s, 2H) , 7.67 (m, 1H), 7.45 (m, 2H) , 7.33 (t, 2H) , 7.22 (dd, 1H) , 6.99 (td, 1H) ppm. MS (ES+) : m/e= .356.20 (M+H); HPLC-Method A Rt 3.00 min. Example 358 (5-Fluoro-lff-indazol-3-yl) - (2-phenyl- quinazolin-4-yl) -amine (XIX-130): ^ NMR (500 MHz, DMSO- d6) 813.2 (s, 1H), II.3 (s, br, 1H) , 8.67 (d, 1H), 8.04 (d, 2H), 7.96 (s, 2H), 7.70 (m, 1H) , 7.58 (dd, 1H), 7.43 (m, 4H), 7.28 (td, 1H) ppm. MS (ES+) 356.20 (M+H); HPLC- Method A, Rt 3.00 min. Example 359 (5,7-Difluoro-lff-indazol-3-yl) - (2-phenyl- quinazolin-4-yl) -amine (III-131): 1H NMR (500 MHz, DMSO- d6) 813.7 (s, 1H), 8.65 (d, 1H), 8.04 (d, 2H) , 7.95 (s, 2H), 7.68 (m, 1H) , 7.45 (m, 1H) , 7.35 (m, 4H) ppm. MS (ES+) : m/e= 374.17 (M+H); HPLC-Method A, Rt 3.07 min. Example 360 (Iff-Indazol-3-yl) - [2- (3-trifluoromethyl- phenyl)-quinazolin-4-yl] -amine (III-132) : ^ NMR (500MHz, DMSO-d6) ? 7.06 (t, 1H), 7.42 (t, 1H), 7.59 (d, 1H) , 7.63 (t, 1H), 7.66 {d, 1H) , 7.71 (m, 1H) , 7.80 (d, 1H) , 7.98 (m, 2H), 8.33 (s, 1H) , 8.46 (d, 1H) , 8.71 (d, 1H) , II.04 (br. S, 1H), 12.97 (s, 1H); El-MS 406.1 (M+l) ; HPLC- Method A, Rt 3.15 min. Example 361 (2-Phenyl-quinazolin-4-yl) - (lH-pyrazolo [4,3- b]pyridin-3-yl)-amine (XII-133): 1H NMR (500 MHz, DMSO-d6) ?13.3 (s, br, 1H) , II.4 (s, br, 1H) , 8.78 (d, 1H) , 8.58 (dd, 1H) , 8.24 (d, 1H), 8.10 (m, 2H), 7.95 (d, 2H) , 7.86 (t, 1H) , 7.56 (m, 2H) , 7.44 (t, 2H) ppm. MS (ES+) 339.II (M+H) ; HPLC-Method A, Rt 2.63 min. Example 362 [5- (3-Methoxy-phenyl) -6-oxo-5, 6-dihydro-1H- pyrazolo [4,3-c] pyridazin-3-yl] - (2-phenyl-quinazolin-4- yl)-amine (III-134) : 1H NMR (500 MHz, MeOH-d4) ?8.65 (d, 1H), 8.17 (m, 3H), 8.10 (d, 1H), 7.90 (t, 1H) , 7.75 (t, 1H), 7.58 (m, 2H), 7.25 (t, 1H), 6.95 (m, 2H) , 6.85 (d, 1H), 6.80 (s, 1H), 3.64 (s, 3H) ppm. MS (ES+) : m/e= 462.2(M+H). Example 363 (6-Oxo-5-phenyl-5,6-dihydro-lH-pyrazolo[4,3- c]pyridazin-3-yl) - (2-phenyl-quinazolin-4-yl) -amine (III- 135): 1H NMR (500 MHz, MeOH-d4) ?8.61 (d, 1H) , 8.13 (m, 3H) , 8.05 (d, 1H), 7.85 (t, 1H), 7.70 (t, 1H) , 7.58 (m, 2H), 7.32 (m, 5H), 6.79 (s, 1H) ppm. MS (ES+) : m/e« 432.2(M+H). Example 3 64 [5- (4-Methoxy-phenyl) -6-oxo-5, 6-dih.ydro-lH- pyrazolo [4,3-e]pyridazin-3-yl] - (2-pnenyl-quinazolin-4- yl)-amine (III-136): MS (ES+) 462.2(M+H). Example 365 [5- (2,4-Dichloro-phenyl) -6-oxo-5, 6-dihydro- lH-pyrazolo[4,3-e]pyridazin-3-yl] - (2-phenyl-quinazolin-4- yl)-amine (III-137): 1H NMR (500 MHz, MeOH-d4) ?8.63 (d, 1H) , 8.17 (m, 4H), 7.89 (t, 1H), 7.73 (t, 1H), 7.61 (t, 2H), 7.57 (d, 1H), 7.32 (m, 1H) , 7.21 (d, 1H) , 6.84 (s, 1H) ppm. MS (ES+) : m/e= 500.1(M+H). Exaaple 366 [6-0X0-5- (3-trifluoromethyl-phenyl) -5, 6- dihydro-lH-pyrazolo[4,3-c]pyridazin-3-yl] - (2-phenyl- quiaazolin-4-yl) -amine (III-138) : XH NMR (500 MHz, MeOH- d4) 58.55 (d, 1H), 8.19 (d, 2H) , 7.92 (m, 2H), 7.65 (m, 3H), 7.45 (t, 2H), 7.25 (t, 1H), 7.13 (t, 1H), 7.05 (t, 1H), 6.75 (s, 1H) ppm. MS (ES+) : m/e«= 500.2 (M+H) . Example 367 [6-Oxo-5- (4-Pbenoxy-pheayl) -5, 6-dihydro-lH- pyrazolo [4, 3-c]pyridazin-3-yl] - (2-phenyl-qu.iaazolln.-4- yl)-amine (III-139): MS (ES+) 524.3(M+H). • Example 368 £5- (4-Chloro-phenyl) -6-oxo-5, 6-dihydro-lH- pyrazolo [4,3-eJpyridazi»-3-yl3 - (2-phenyl-guinazolin-4- yl)-amiae (III-140): MS (ES+) 466.2(M+H). Example 369 (2-imidazol-l-yl-quinazolin-4-yl) - (1H- indazol-3-yl)-amine (III-141) .- XH HMR (500MHz, DMSO-d6) 8 7.10 (t, 1H), 7-44 (t, 1H), 7.50 (i>r. s, 1H) , 7.60 (d, 1H), 7.72 (tn, 2H), 7.77 (m, 1H) , 7.88 (d, 1H) , 7.98 1H), 8.73 (d, 1H), 8.96 (s, 1H), II-23 (s, 1H) , 13.06 (s, 1H) ; El-MS 328.1 (M+l) ; HPLC-Method A, Rt 2.93 min. T^a^le 370 (lH-Indazol-3-yl) - [2- (2-xnfitbyl-imidazol-l-yl- qainazolin-4-yl]-amine (III-142) : XH NMR (500MHz, DMSO-d6) 8 2.48 (S, 3H), 7.10 (t, 1H), 7-43 (t, 1H), 7.57 (d, 1H), 7.60 (d, 1H), 7.67 (d, 1H), 7.76 (td, 1H), 7.86 (d, 1H), 7.91 (d, 1H) , 8.01 (td, 1H) , 8.72 (d, 1H) , II.15 (s, 1H) , 13.10 (s, 1H) ; El-MS 342.1 (M+l) ; HPLC-Method A, Rt 3.06 min. Example 371 (lff-Indazol-3-yl) - (2-piperidin-l-yl- quinazolin-4-yl)-amine- (III-143) : H NMR (SOOMHz, DMSO-d6) 8 1.48 (m, 6H) , 3.60 (mf 4H) , 7.II (t, 1H), 7.52 (t, 1H) , 7.55 (d, 1H), 7.64 (d, 1H) , 7.69 (d, 1H), 7.75 (d, 1H) , 7.90 (t, 1H) , 8.58 (d, 1H), II.82 (br. s, 1H) , 13.25 (s, 1H) ; EI-MS 345.1 (M+l); HPLC-Method A, Rt 3.03 min. Example 372 (lH-Indazol-3-yl) - [2- (oetah.ydro-quinolin-1- yl)-quinazolin-4-yl]-amine (III-144): XH NMR (500MH2, DMSO-d6) 8 0.6-1.9 (m, 13 H) , 3.15 (a, 1H) , 3.25 (m, 1H), 4.0 (m, 1H), 7.10 (t, 0.5H), 7.12 (t, 0.5H), 7.55 (m, 2H), 7.66 (d, 0.5 H), 7.69 (d, 0.5 H), 7.77 (d, 1H) , 7.91 (t, 1H), 8.55 (d, 0.5 H) , 8.59 (d, 0.5 H), II.46 (s, 0.5 H) , II.54 (s, 0.5 H)# II.78 (s, 0.5 H) , II.84 (s, 0.5 H) , 13.10 (S, 0.5 H), 13.12 (s, 0.5 H); EI-MS 399.3 (M+l); ? HPLC-Method A, Rt 3.37 min. Example 373 (lff-Indazol-3-yl) - [2- (2# 6-dimethyl-morpholin- . 4-yl)-quinazolia-4-yl]-amine (III-145)-. XS. NMR (500MHz, DMSO-d6) 8 1.0 (m, 6H), 4.0 (m, 6H), 7.12 (t, 1H) , 7.41 . (td, 1H), 7.56 (t, 1H), 7.58 (d, 1H), 7.68 (dd, 1H), 7.77 (t, 1H) , 7.93 (t, 1H) , 8.60 (d, 1H) , II.69 (s, 1H) , 13.16 (s, 1H) ; EI-MS 375.3 (M+l); HPLC-Method A, Rt 2.93 min. Example 374 (5-Methyl-2fl'-pyrazol-3-yl) - (2-phenyl- pyrimidin-4-yl)-amiixe (IV-1)-. mp 245-246°C; XH NMR (DMSO) 8 2.26 (3H, s), 6.32 (1H, br s), 7.07 (1H, br s), 7.48- 7.54 (3H, m) , 8.33-8.39 (3H, m), 9.87 (1H, s), 12.03 (1H, s); IR (solid) 1628, 1589, 1579, 1522, 1479, 1441, 1393, 1336; MS 252.2 (M+H)+. Example 375 [6- (4-Acetamidophenylsulfanyl)-2-phenyl- pyrimidin-4-yl] - {5-methyl-2H-pyrazol-3-yl} -amine (IV-3) : A suspension of Fenclorim (4, 6-dichloro-2- phenylpyrinddine) (0. lg, 0.44 mmol) , 3 -amino-5- methylpyrazole (0.045 g, 0.47 mmol), N, N- diisopropylethylamine (0.08 ml, 0.47 nmol) and sodium iodide (0.067 g, 0.44 mmol) in n-butanol (5 ml) were heated at II7 oC for 18 hours. The solvent was removed in vacuo and the crude product purified by flash chromatography (silica gel, 3:2 Petrol:EtOAc) to afford 0.037 g (29 % yield) of (6-Chloro-2-phenyl-pyrimidin-4- yl) - (5-methyl-2H-pyrazol—3-yl) -amine as a off-white solid. A suspension of the above pyrimidine (0.037 g, 0.13 mmol) and thioacetamidothiophenol (0.108 g, 0.64 mmol) in tert-butanol was heated at 85 °C under nitrogen for 2 days. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. The concentrate was dissolved in EtOAc, and washed with NaHCO3 (sat, aq.) . The organic layer is concentrated in vacuo, and the crude product by preperative HPLC. The residual disulfide that still remained in the mixture after HPLC may be removed by precipitation from EtOAc and filtration. The mother liquor was concentrated to afford IV-3 (7mg, 13 % yield) as an off-white solid: mp 235- 236°C; H NMR (DMSO) 5 2-10 (3H, s) , 2.21 (3H, s) , 6.33 (1H, br s), 7.50 (3H, m), 7.7-7.59 (2H, m), 7.76-7.78 (2H, m), 8.25 (2H, m) , 9.72, 10.26 and II.93 (3 H, 3 x br s); IR (solid) 1669. 1585, 1551, 1492, 1392, 1372, 1312, 1289, 1259, II74, II02, 1089, 1027, 1015, 984; MS 417.3 (M+H) + . Example 376 [2- (4-Methylpiperidin-l-yl) -pyrimidin-4-yl] - (5-methyl-2H-pyrazol-3-yl)-amine (IV-4) : mp 215-216°C; 1H NMR (CD3OD) ? 0.96 (3H, d) , 1.16 (2H, m), 1.66 (3H,- m) , 2.27 (3H, s), 2.86 (2H, t) , 4.58 (2H, m), 4.78 (2H, exch.protons) , 6.13 (2H, m) , 7.83 (1H, d) ; IR (solid) 1593, 1550, 1489, 1436, 1331, 1246, 1231; MS 273.1 (M+H)+. Example 377 [2- (4-Methylpiperidin-l-yl) -5-nitropyrimidin- 4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (IV-5) : mp 185- 187°C; 1H NMR (DMSO) 5 0.93 (3H, d) , 1.06-1.18 (2H, m) , 1.68-1.80 (3H, m) , 2.26 (3H, s), 3.01-3.12 (2H, m), 4.63 (1H, d), 4.80 (1H, d), 6.39 (1H, s) , 9.00 (1H, s), 10.41 (1H, s), 12.36 (1H, s); IR (solid) 1589, 1517, 1479, 1446, 1346, 1317, 1246, 1222, 1055; MS 318.2 (M+H)+. Example 378 [5-Amino-2- (4-Methylpiperidin-l-yl) - pyrimidin-4-yl] - (5-methyl-2H'-pyrazol-3-yl) -amine (IV-6) : To a solution of IV-5 (48 mg, 0.151 mmol) in ethanol (2.0 mli) was added tin dichloride dihydrate (171 mg, 0.756 mmol) and the resulting mixture heated at reflux for 3 hours. The reaction was cooled to room temperature and poured onto a mixture of 1M NaOH: dichloromethanerpropanol (18:8:4mL). and stirred for 15 minutes. The layers were separated and the aqueous layer extracted twice with dichloromethane. The combined organic layers -were concentrated in vacuo and the residue purified by flash chrpmatography (silica gel, gradient dichloromethane:MeOH) to afford IV-6 as a grey solid (27mg, 63%): ^ NMR (DMSO) 8 0.88-1.04 (5H, m) , 1.55-1.62 (3H, m), 2.21 (3H, s), 2.70 (2H, m), 3.36 (2H, m), 4.40 (2H, m), 6.37 (1H, s), 7.49 (1H, s), 8.40 (1H, s) , II.92 (1H, br s); MS 288.2 (M+H)+. Example 379 [5-Amino-6-methyl-2- (4-methylpiperidin-l-yl) - pyrimidin-4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (IV-7) : mp 172-175°C; 1H NMR (DMSO) ? 0.90 (3H, d) , 1.03 (2H, m) , 1.52-1.62 (3H, m) . 2.13 (3H, s) , 2.20 (3H, s) , 2.69 (2H, m), 3.92 (2H, br s) , 4.44 (2H, d) , 6.35 (1H, s), 8.41 (1H, S), II.85 (1H, br S) ; IR (solid) 1612, 1589, 1489, 1446, 1317; MS 302.5 (M+H)+. Example 380 16-Methyl-2- (4-methyl-phenyl) -pyrimidin-4- yl]- (5-phenyl-2H-pyrazol-3-yl) -amine (IV-10) : MS 342.34 (M+H) ; HPLC-Method E, Rt 1.334 min. Example 381 [2- (4-Chloro-phenyl) -6-methyl-pyrimidin-4- yl]-(5-furan-2-yl-2H-pyrazol-3-yl)-amine (IV-II) : MS 352.II (M+H); HPLC Method E, Rt 1.194 min. Example 382 5-Puran-2-yl-2H-pyrazol—3-yl) - (6-methyl-2- phenyl-pyrinddin-4-yl)-amine (IV-12) : MS 318.21 (M+H) ; HPLC-Method E, 1.192 min. Example 383 [6-Methyl-2- (4-trifluoromethyl-phenyl) - pyrimidin-4-yl] - (5-phenyl-2-yl-2H-pyrazol—3-yl) -amine (IV-13) : MS 396.24 (M+H); HPLC-Method E, Rt 1.419 min. Example 384 (5-Fur an-2-yl-2H-pyrazol—3-yl) - [6 -methyl -2- (4-trif luoremethyl-phenyl) -pyrimidin-4-yl] -amine (IV-14) : MS 386.08 (M+H); HPLC-Method E 1.347 min. Example 385 [2- (2,3-Pihydro-benzo[l,4] dioxin-2-yl) -6- methyl-pyrimidin-4-yl] - (5-furan-2-yl-2H-pyrazol—3-yl) - amine (IV-15): MS 376.18 (M+H); HPLC-Method E, Rt 1.181 min. Example 386 [2- (2,3-Dihydro-bezo[l,4]dioxin-2-yl) -6- ethyl-pyrimidin-4-yl] - (5-methyl-2ff-pyrazol—3-yl) -amine (IV-16): MS 338.17 (M+H); HPLC-Method E, Rt 1.082 min. Example 387 (6-Ethyl-2-phenyl-pyrimidin-4-yl) - (5-methyl- 2H-pyrazol-3-yl) -amine (IV-17) : MS 280.18 (M+H); HPLC- Method E, Rt 1.024 min. Example 388 {6-Methyl-2-phenyl-pyrimidin-4-yl) - (5-phenyl- 2H-pyrazol-3-yl)-amine (IV-19) : MS 328.51 (M+H); HPLC- Method E, Rt 1.192 min. Example 389 [6-Ethyl-2-(4-trifluoromethy 1 -pheny1)- pyrimidin- 4 -yl] - (5 -methyl - 2ff-pyrazol—3 -yl) - amine (XV- 20): MS 348.5 (M+H); HPLC-Method E, Rt 1.224 min. Example 390 (5-Furan-2-yl-2H-pyrazol—3-yl) - [6-methyl-2- (4-methyl-pheny1)-pyrimidin-4-yl]-amine (IV-21) : MS 332.23 (M+H); HPLC-Method E, Rt 1.139 min. Example 391 (6-Methoxymethyl-2-phenyl-pyrimidin-4-yl) - (5- methyl-2H-pyrazol-3-yl)-amine (IV-22) : MS 296.31 (M+H) ; HPLC-Method E, Rt 0.971 min. Example 392 (5,6-Dimethyl-2-phenyl-pyrimidin-4-yl)-(5- methyl-2H-pyrazol-3-yl) -amine (IV-23) : MS 280.2 (M+H) ; HPLC-Method E, Rt 0.927 min. Example 393 (6-Methyl -2 -phenyl -pyrimidin-4 -yl) - (5-methyl- Zff-pyrazol-3-yl) -amine (XV-24) : MS 266.18 (M+H); HPLC- Method E, Rt 0.925 min. Example 394 [6-Ethyl-2- (4-methyl-phenyl) -pyrinidin-4-yl] - (5-methyl-2H-pyrazol-3-yl)-amine (IV-25): MS 294.46 (M+H); HPLC-Method E, Rt 1.174 min. Example 395 [2- (4-Chloro-phenyl) -6-ethyl-pyri»idin-4-yl] - {5-methyl-2ff-pyrazol-3-yl)-amine (IV-26) : MS 314.42 (M+H); HPLC-Metnod E Rt 1.213 min. Example 396 (5-Methyl-lH-pyrazol-3-yl) - (6-methyl-2-p- tolyl-pyrimidin-4-yl)-amine (IV-27): MS 280.45 (M+H); HPLC-Method E, Rt 1.135 min. Example 397 (JJB-Indazol- 3 -yl) - (6-methoxymethyl-2 -phenyl- pyrimidin-4-yl)-amine (XV-28) : XH NMR (500 MHz, DMSO) 8 3.57 (3H, s) , 4.65 (2H, s) , 7.23 (1H, J==7.5 Hz, t) , 7.52 (1H, J=7.6 Hz, t), 7.63 (4H, m) , 7.75 (1H, br), 8.13 (1H, J=5.5 Hz, br d), 8.44 (1H, J=5.7 Hz, br d) , 10.6 (1H, br), 12.8 (1H, br s) ppm; HPLC-Method A, Rt 2.944 min; MS (FIA) 332.1 (M+H)+. Example 398 {5-Methyl-2H-pyrazol-3-yl) - (2-pyxidin-4-yl- thieno 13,2-d]pyrimidin-4-yl)-amine (IV-29): XH NHR (DMSO) 6 2.34 (3H, s), 6.66 (1H, s), 7.53 (1H, d) , 7.84 (1H, d), 8.32 (2H, d) , 8.70 (2H, d); MS 309.6 (M+H)+. Example 399 (5-Methyl-2ff-pyrazol-3-yl) - (2-pheayl- pyrido[3,4-d]pyrimidin -4-yl)-amine (IV-30) : np 225°C; XH NMR (DMSO) 5 2.35 (3H, s), 6.81 (1H, s), 7.50-7.63 (3H, m) , 8.45-8.52 (2H, m) , 8.54 (1H, d) , 8.62 (1H, d) , 9.20 (1H, s), 10.79 (1H, s), 12.38 (1H, br B); IR (solid) 2958, 2917, 2852, 1593, 1565, 1524, 1467, 1450; MS 303.2 (M+H) + . Example 400 (5-Methyl-2H-pyrazol-3-yl) - (2-phenyl- pyrido[2,3-d]pyrimidin-4-yl)-amine (IV-31) : To a solution of 4-chloro-2-phenyl-pyrido[2, 3- d]pyrimidine (J. Pharm. Belg., 29, 1974, 145-148) (109mg, 0.45 mol) in THF (15 mL) was added 3-amino-5-methyl pyrazole (48 mg, 0.5 mmol) and the resulting mixture heated at 65 °C overnight. The mixture was cooled to room temperature and the resulting suspension was filtered and washed with Et2O. The solid was dissolved in a mixture EtOH: water and the pH adjusted to pH 7. The aqueous was extracted twice with ethyl acetate and the combined organic layers were dried (MgSO4) , filtered, and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, DCM-MeOH gradient) to afford IV-31 as an off -white solid (69 mg, 50%): mp 234°C; ^H NMR (DMSO) 6 2.14 (3H, s), 5.99 (1H, s), 7.20-7.40 (3H, m) , 7.40-7.50 (3H, m), 8.60 (1H, d), 8.79 (1H, d), 12.82 (1H, br s) ; IR (solid) 2957, 2921, 2857, 1644, 1560, 1459, 1427; MS 303.2 (M+H)+. Example 401 (5-Cyclopropyl-2H-pyrazol-3-yl) - (2-phenyl- pyridor3,4-d]pyrimidin-4-yl)-amine (IV-32) : off-white solid, mp 232-233°C; ^ NMR (DMSO) 6 0.70-0.85 (2H, m) , 0.90-1.05 (2H, m) , 1.05-2.07 (1H, m) , 6.75 (1H, s), 7.50- 7.75 (3H, m) , 8.40-8.70 (4H, m), 9.20 (1H, s), 10.80 (1H, s) , 12.41 (1H); IR (solid) 3178, 1601, 1573, 1532, 1484, 1452, 1409, 1367, 1328, 802, 781, 667; MS 329.2 (M+H)+. Example 402 [2- (4-Methylpiperidin-l-yl) -purin-4-yl] - (5- methyl-2H-pyrazol-3-yl) -amine (IV-33) : To a suspension of 2,4-dichloro-purine (2.0 g, 10.6 mmol) in anhydrous ethanol (10 mL) was added 5-methyl-lH-pyrazol-3-yl amine (2.05 g, 21.2 mmol) . The resulting mixture was stirred at room temperature for 48 h. The resulting precipitate was collected by filtration, washed with ethanol, and dried under vacuum to afford 1.524 g (58% yield) of (2- chloro-purin-4-yl) - (5-methyl-lH-pyrazol-3-yl) -amine which was used in the next step without further purification. To a solution of (2-chloro-purin-4-yl) - (5-methyl-1H- pyrazol-3-yl) -amine (200 mg, 0.80 mmol) was added 4- methylpiperidine (4 mL, 8.01 mmol) and the reaction mixture heated at reflux overnight. The solvent was evaporated and the residue dissolved in a mixture EtOH:water (1:3, 4 mL). Potassium carbonate (57mg, 0.41 mmol) was added and the mixture was stirred at room temperature for 2 hours. The resulting suspension was filtered, washed with water (x2) and rinsed with Et2O (x2) to afford IV-33 as a white solid (225mg, 90%): mp >300°C; 1H NMR (DMSO) ? 0.91 (3H, d), 1.10 (2H, m), 1.65 (3H, m) , 2.24. (3H, s), 2.84 (2H, m), 4.60 (2H, m) , 6.40 (1H, s), 7.87 (1H, m), 9.37-9.59 (1H, m) , 12.03-12.39, (2H, m); IR (solid) 1651, 1612, 1574, 1484, 1446, 1327, 1317, 1255, 1203; MS 313.3 (M+H)+. Example 403 (5-Cydopropyl-2H-pyrazol-3-yl) - [2- (4- methylpiperidin-1-yl) -pyrrolo[3,2-d]pyrimidin-4-yl] -amine (IV-34) : white solid; 1H NMR (DMSO) ?-0.65 (2H, m) , 0.91- 0.96 (5H, m), 1.08 (2H, m), 1.58-1.64 (3H, m), 1.89 (1H, m), 2.77 (2H, t), 4.57 (2H, d), 6.09 (1H, s), 6.38 (1H, s) , 7.33 (1H, s), 9.42 (1H, s) , 10.65 (1H, s) , 12.02 (1H, br s); MS 338.3 (M+H)+. Example 404 [6-Benzyl-2-phenyl-5,6,7,8-tetrahydro- pyrido [4,3-d]pyrimidin-4-yl] - (5-fluoro-lff-indazol-3-yl) - amine (IV-35) : 1H NMR (500 MHz, DMSO-d6) ?13.0 (s, 1H) , 10.4 (s, br, 1H) , 9.73 (s, 1H, TFA-OH) , 8.00 (d, 2H) , 7.64 (m, 2H) , 7.59 (dd, 1H) , 7.52 (m, 3H) , 7.41 (t, 1H) , 7.31 (m, 3H), 7.14 (dd, 1H) , 4.58 (s, 2H), 4.35 (br, 2H) , 3.74 (m, 2H) , 3.17' (s, 2H) ppm. MS (ES+) : m/e= 451.30 (M+H) ; HPLC-Method A, Tret 2.96 min. Example 405 (5-Fluoro-lS-indazol-3-yl) - (2-pheayl-5, 6,7,8- tetrahydro-pyrido [4,3-d]pyriioidin-4-yl) -amine (IV-36) : Prepared from IV-35 (0.13 mmol) by treatment, with an equal weight of Pd/C (10%) in 4.4% HCOOH in MeOH at room temperature for 12 h. The mixture was filtered through, celite, the filtrate was evaporated, and crude product was purified by HPLC to afford IV-36 as yellow solid in 35% yield. XH NMR (500 MHz, DMSO-d6) 812.9 (s, 1H) , 9.06 (s, 1H) , 7..99 (d, 2H) , 7.57 (dd, 1H) , 7.34 (m, 1H) , 7.28 (m, 3H), 7.22 (d, 1H), 3.83 (s, 2H),. 3.05 (m, 2H), 2.72 (m, 2H) ppm. MS (ES+) : m/e= 361.20 (M+H); HPLC-Method A, Tret 2.68 min. Example 406 (5-Methyl-2H-pyrazol—3-yl) - (3 -phenyl- isoquinolin-1-yl)-amine (V-l) : To a solution of 1-chloro- 3-phenylisoquinoline (J. Het. Chem., 20, 1983, 121- 128) (0.33g, 1.37 mmol) in DMF (anhydrous, 5 mL) was added 3-amino-5-methylpyrazole (0.27g, 2.74 mmol) and potassium carbonate (0.57g, 4.13 mmol) and the resulting mixture was heated at reflux for 6 hours. The reaction mixture was then cooled and solvent removed in vacuo. The residue was extracted twice with ethyl acetate and the combined organic layers washed with brine, dried (MgS04) , filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, gradient DCM-MeOH) to afford V-l as a colourless oil; JH NMR (MeOD) 5 2.23 (3H, s) , 5.61 (1H, s), 7.41 (1H, m), 7.52(2H, m), 7.62 (1H, m) , 7.81(1H, m), 8.07 (1H, d) , 8.19(2H, m) , 8.29(1H, s) , 8.54 (1H, d) ; MS 301.2 (M+H) + . Example 407 (lH-Indazol-3-yl) - [3- (2-trifluoromethyl- phenyl)-isoquinoline-1-yl]-amine (V-2) : A solution of 1- chloro-3-(2-trifluoronethyl-phenyl)-isoquinoline (100 mg, 0.326 mmol) and lH-indazol-3-ylamine (86 mg, 0.651 ramol) in ethanbl (3 mL) was heated at 160 C and the solvent evaporated with a stream of nitrogen. The remaining oil was then heated at 160 C for 18 hours under nitrogen. The resulting melt was dissolved in 5% methanol:dichloromethane (50 mL) , washed with saturated aqueous sodium bicarbonate (1 x 25 mL) then dried over magnesium sulfate. Purification by silica gel chromatography (25% to 50% hexane:ethyl acetate) afforded V-2 as a yellow solid (35 mg, 27%). 1H NMR.(500 MHz, d6- DMSO) ? 9.78 (br s, 1H), 8.62 (d, 1H) , 7.9-7.85 (m, 1H) , 7.78-7.72 (m, 1H), 7.70-7.68 (m, 1H) , 7.65-7.62 (m, 1H) , 7.60-7.55 (m, 1H) , 7.52-7.45 (m, 3H) , 7.41-7.38 (m, 1H) , 7.28-7.25 (m, 1H) , 7.18 (s, 1H) , 6.95-6.92 (m, 1H) , 5.76 (s, 1H) ; LC-MS (ES+) m/e= 405.18 (M+H); HPLC-Method D Rt 2.74 min. Example 408 (5,7-Difluoro-lff-indazol-3-yl) - [3- (2- trifluorometfcyl-phenyl)-isoquinolin-1-yl] -amine (V-3) : Prepared from 5,7-difluoro-lH-indazol-3-ylamineto afford compound V-3 as a yellow solid (90 mg, 63%) . . aH NMR (500 MHz, de-DMSO) 8 13.25 (s, 1H) , 9.92 (br S, 1H) , 8.61 (d, 1H) , 7.9 (d, 1H), 7.81-7.49 (m, 6H) , 7.26-7.2 (m, 2H) , 7.12-7.10 (m, 1H) ; LC-MS (ES+) m/e= 441.16 (M+H) ; HPLC- Method D, Rt 3.58 min. Example 409 (5-Methyl-2H-pyrazol—3-yl) - {2-phenyl- quinolin-4-yl) -amine (V-4) : To a mixture of 4-chloro-2- phenylquinoline (J. Het. Chem., 20, 1983, 121-128) (0.53g, 2.21 mmol) in diphenylether (5 mL) was added 3-amino-5- methylpyrazole (0.43g, -4.42 mmol) and the resulting mixture heated at 200°C overnight with stirring. The reaction mixture was cooled to ambient temperature then petroleum ether (20 mL) was added and the resulting precipitate was isolated by filtration. The crude solid was purified by flash chromatography (SiO2, gradient DCM- MeOH) to afford V-4 as a white solid: mp 242-244°C; aH NMR (DMSO) 8 2.27(3H, s), 6.02(lH, s), 7.47(2H, d), 7.53- 7.40 (2H) brill), 7.67 (1H, m) , 7.92 (1H, m) , 8'09(2H, d) , 8.48(2H, m) , 9.2O(1H, s), 12.17(1H, br s); IR (solid) ' 1584, 1559r 1554, 1483, 1447, 1430, 1389; MS 301.2 (M+H)+. Example 410 (Iff- Xndazol -3-yl)-(2 -phenyl - quinolin- 4 -yl) - amine (V-5) : XH NMR (500 MHz, de-DMSO) 8 12.78 (s, 1H) , 9.50 (s, 1H) , 8.65 (d, 1H), 8.15 (s, 1H), 8.04-7.98 (m, 3H) , 7.94 (s, 1H), 7.78-7.75 (m, 1H) , 7.60-7.40 (m, 6H) , 7.15-7.10 (m, 1H) . LC-MS (ES+) m/e= 337.II (M+H) ; HPLC- Method D, Rt 2.10 min. Example 4II (2-Phenyl-quinolin-4-yl) - (lff-pyrazolo[4,3- b]pyridin-3-yl)-amine (V-6) : H NMR (500 MHz, DMSO-d6) 813.6 (s, 1H) , II.4 (s, 1H), 8.94 (d, 1H), 8.61 (dd, 1H), 8.23 (d, 1H); 8.16 (dd, 1H), 8.12 (t, 1H), 7.89 (t, 1H) , 7.86 (d, 1H), 7.65 (m, 4H), 7.54 (s, 1H), 7.52 (dd, 1H) ppm. MS (ES+) : m/e= 338.II (M+H); HPLC-Method A, HPLC- Method D, Rt 2.91 min. Example 412 (lff-Indazol-3-yl)- [2- (2-trifluoromethyl- phenyl) -quinolin-4-yl] -amine (V-7) : 1H NMR (500 MHz, d6- DMSO) 5 12.68 (s, 1H), 9.51 (s, 1H), 8.7 (d, 1H) , 7.95- 7.89 (m, 2H), 7.83-7.70 (m, 3H), 7.68-7.62 (m, 2H) , 7.60 (s, 1H), 7.55-7.52 (m, 1H), 7.49-7.45 (m, 1H) , 7.40-7.37 (m, 1H), 7.12-7.09 (m, 1H); LC-MS (ES+) m/e= 405.15 (M+H) ; HPLC-Method D Rt 2.25 min. Example 413 (5,7-Difluoro-lH-indazol-3-yl)-[2-(2- trifluoromethyl-phenyl) -quinolin-4-yl] -amine (V-8) : :H NMR (500 MHz, de-DMSO) 8 13.31 (s, 1H) , 9.4.9 (s, 1H) , 8.70- 8.67 (m, 1H), 7.96-7.92 (m; 1H), 7.85-7.66 (m, 7H), 7.63- 7.60 (m, 1H), 7.42-7.40 (m, 1H) . LC-MS (ES+) m/e= 441.18 (M+H); HPLC-Methpd D Rt 2.39 min. Example 414 [2- (2-trifluoroxnethyl-phenyl> -quinolin-4-yl] - (lH-pyrazolo[4,3-b]pyridin-3-yl)-amine (V-9) : JH HMR (500 MHz, DMSO-d6) 513.6 (s, 1H), II.6 (s, br, 1H) , 8.98 (d, 1H) , 8.57 (dd, 1H) , 8.12 (m, 3H), 7.97 (m, 2H), 7.86 (m, , 3H) , 7.49 (dd, 1H), 7.23 (s, 1H) ppm. MS (ES+): m/e= 406.20 (M+H); HPLC-Method A Rt 2.91 min. Example 415 (2-Phenyl-quinazolin-4-yl)-(2H- [1,2,4]triazol-3-yl)-amine (IX-154): off-white solid, mp 266-267C; XH NMR (DMSO) 5 7.50-7.70 (4H, m) , 7.85-8.00 (2H, m), 8.15-8.25 (2H, m), 8.37-8.45 (2H, m), 8.58 (1H, d), 13.90 (1H, br s); IR (solid) 3344, 3059, 1630, 1609, 1570, 1557, 1543, 1501, 1495, 1445, 14II, 1355, 1326, 1267, II82, 1053, 1038, 760, 676, 667, 654; MS 289.2 (M+H)+. Example 416 (5-Methyl-2ff-[1,2#4]triazol-3-yl) -(2-phenyl- quinazolin-4-yl) -amine (IX-155) : XH NMR (500 MHz, DMSO- d6) 5 8.59 (s, 1H), 8.42 (d, J = 6.7 Hz, 2H), 7.79 (m. 4H), 8.03 (m, 2H), 7.74 (m, 4H), 2.51 (s, 3H) ppm. MS (ES+): m/e= 303.08 (M+H); HPLC-Method A, Rt 2.64 min. Example 417 (2H-[1,2,4]-Triazol-3-yl) - 12-(2- trifluoromethylphenyl) -guinazolin-4-yl] -amine (IX-47) : Pale yellow solid (52% yield). 1H NMR (500 MHz, DMSO-d6) ? 8.54 (s, 1H), 8.15 (s, br, 1H), 7.91 (t, 1H) , 7.85 (m, 2H) , 7.76 (m, 3H), 7.66 (t, 1H) ppm. MS (ES+) : m/e= 357.13 (M+H); (ES-):m/e= 355.15 (M-H) ; HPLC-Method A, Rt 2.81 min. Example 418 (5-Methyl-2H- [1/2,4]triazol-3-yl)-[2-(2- trifluoromethylphenyl) -guinazolin-4-yl] -amine (IX-38) : Pale yellow solid (54% yield). 1H NMR (500 MHz, DMSO-d6) ?8.44 (s, br, 1H), 7.92 (m, 3H) , 7.84 (m, 1H), 7.77 (m, 2H) , 7.68 (t, 1H), 2.28 (s, 3H) ppm. MS (ES+) : m/e= 371.14 (M+H); (ES-): m/e= 369.18 (M-H); HPLC-Method A, Rt 2.89 min. Example 419 (5-Methylsulfanyl-2H-[1,2,4]triazol-3-yl)-[2- (2-trifluorometbylphenyl) -guinazolin-4-yl] -amine (IX- 156): Pale yellow solid (65% yield). 2H NMR (500 MHz, DMSO-d6) 5 8.56 (br, 1H), 7.90 (t, 1H), 7.84 (m, 2H), 7.78 (m, 2H) , 7.67 (m, 2H) , 2.51 (s, 3H, buried by DMSO) ppm. MS (ES+): m/e= 403.12 (M+H); (ES-): m/e= 401.16 (M-H); HPLC-Method A, Rt 3.20 min. Example 420 (IE-[1,2,4]Triazol-3-yl) -[3-(2- trifluoromethyl-phenyl)-isoquinolin.-1-yl]-amine (IX-175) : A solution of l-chloro-3-(2-trifluoromeybyl-phenyl)- isoquinoline (0.326 mmol) and 2.H- [1,2,4] triazol-3-ylamine (0.651 mmol) in ethanol (3 mL) was heated at 160°C and the solvent evaporated with' a stream of nitrogen. The remaining oil was then heated at 160°C for 18 hours under nitrogen. The resulting melt was dissolved in 5% methanol/dichloroinethane (50 mL) , washed with saturated aqueous sodium bicarbonate (1 x 25 mL) then dried over magnesium sulfate. Purification by silica gel chromatography afforded IX-175 as a colorless oil (4% yield). XH NMR (500 MHz, CDC13) 5 9.18 (d, 1H) , 8.82 (s, 1H), 7.90 (d, 1H), 7.85-7.75 (m, 3H), 7.71-7.62 (m, 3H) , 7.60-7.55 (m, 2H), 4.42-4.35 (m, 1H). LC-MS (ES+) 356.16 (M+H) ; HPLC-Method D, Rt 3.55 min. Example 421 (2-Phenyl-quinolin-4-yl) -(Iff-[1,2,4]triazol- 3-yl)-amine (IX-176): Pale yellow solid (30% yield). 2H NMR (500 MHz, dg-DMSO) 8 13.82 (s, 1H) , 9.91 (S, 1H) , 8.80 (s, 1H) , 8.70-8.65 (m, 1H),..8.55 (s, 1H) , 8.15-8.12 (m, 2H), 8.03-7.98 (m, 1H), 7.75-7.72 (m, 1H), 7.57-7.49 (m, 3H) . LC-MS (ES+) m/e= 288.II (M+H); HPLC-Method D, Rt 1.55 min. Example 422 (Iff-[1,2,4]triazol-3-yl)-[2-(2- trifluoromethyl-phenyl) -quinolin-4-yl] -amine (IX-177) : Pale yellow solid (46% yield) . XH NMR (500 MHz, ds-DMSO) 8 13.70 (s, 1H), 9.98 (s, 1H), 8.70 (d, 1H), 8.49 (s, 1H), 8.30 (s, 1H), 7.94-7.88 (m, 2H), 7.30-7.68 (m, 3H) , 7.64-7.56 (m,. 2H) . LC-MS (ES+) m/e= 356.18 (M+H); HPLC- Method D, Rt 1.68 min. Example 423 (l-H-Xndazol-3-yl) - [5-methyl-6-morplxolin-4- yl-2- (2-trifluorometliyl-phenyl) -pyrimidin-4-yl] -amine (II-251) : Colorless film; 2 % yield; ^-.H-NMR (500 MHz, CD3OD) 8 7.84 (m, 2H), 7.71 (m, 3H), 7.41 (t, 2H) , 7.14 (m, 1H), 3.74 (m, 4H), 3.69 (m, 4H), 1.24 (s, 3H) ppm; HPLC-Method A Rt 3.26 min; MS (FIA) 455.1 (M+H). BIOLOGICAL TESTING The activity of the compounds as protein kinase inhibitors may be assayed in vitro, in vivo or in a cell line. In vitro assays include assays that determine inhibition of either the phosphorylation activity or ATPase activity of the activated protein kinase. Alternate in vitro assays quantitate the ability of the inhibitor to bind to the protein kinase. Inhibitor binding may be measured by radiolabelling the inhibitor prior to binding, isolating the inhibitor/protein kinase complex and determining the amount of radiolabel bound. Alternatively, inhibitor binding, may be determined by running a competition experiment where new inhibitors are incubated with the protein kinase bound to known radioligands. BIOLOGICAL TESTING EXAMPLE 1 Ki DETERMINATION FOR THE INHIBITION OF GSK-3 Compounds were screened for their ability to inhibit GSK-3P (AA 1-420) activity using a standard coupled enzyme system (Fox et al. (1998) Protein Sci. 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5) , 10 mM MgCl2, 25 mM NaCl, 300 ?M NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 ?M ATP (Sigma Chemicals, St Louis, MO) and 300 ?M peptide (HSSPHQS(PO3H2)EDEEE, American Peptide, Sunnyvale, CA) . Reactions were carried out at 30 °C and 20 nM GSK-3?. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 ?M NADH, 30 ?g/ml pyruvate kinase and 10 ?g/ml lactate dehydrogenase. An assay stock buffer solution was prepared containitig all of the reagents listed above with the exception of ATP and the test compound of interest. The assay stock buffer solution (175 ?l) was incubated in a 96 well plate with 5 ?l of the test compound of interest at final concentrations spanning 0.002 ?M to 3 0 ?M at 30 °C for 10 min. Typically, a 12 point titration was conducted by preparing serial dilutions (from 10 mM compound stocks) with DMSO of the test compounds in daughter plates. The reaction was initiated by the addition of 20 ?l of ATP (final concentration 20 ?M) . Rates of reaction were obtained using a Molecular Devices Spectramax plate reader (Sunnyvale, CA) over 10 min at 30 °C. The Ki values were determined from the rate data as a function of inhibitor concentration. The following compounds were shown to have Ki values less than 0.1 )M for GSK-3: compounds II-l, II- 105, II-33, II-34, II-36, II-39, II-38, II-39, II-40, II- 41, II-42, II-46, II-57, II-59, II-60, II-61, II-62, II- 63, II-64, II-66, II-67, II-69, II-70, II-53, II-71, II- 99, II-73, II-74, II-75, II-76, II-77, II-7, II-8, II-9, II-10, II-24, II-19, II-78, II-54, II-79, II-80, II-81, . II-82, II-83, II-84, II-56, II-86, II-20, II-25, II-26, II-85, II-21; II-27, II-28, II-87, II-88, II-29, II-II, II-12, II-30, II-31, II-13, II-14, II-15, II-16, II-17, II-18, II-79, II-23, II-2, II-90, II-91, II-92, II-93, II-3, II-4, II-5, II-6, II-94, II-95, II-96, II-107, II- 108, II-109, II-II0, II-124, II-125, II-1II, II-II2, II- II3, II-II4, II-II5, II-II6, II-II7, II-II8, II-II9, II- 120, II-121, II-208, III-8, III-7, III-9, III-37, III-38, III-39, III-40, III-42, III-45, III-46, III-47, III-48, III-4-9, III-51, III-52, III-53, III-54, III-55, III-56, III-57, III-58, III-59, III-60, III-61, III-62, III-63, III-30, III-65, III-66, III-67, III-70, III-73, III-31, III-75, III-76, III-77, III-33, III-34, III-1D6, III-108, III-109, III-lll, III-35, III-II6, III-II7, III-II8, III- II9, III-120, III-121, III-127, III-128, IU-141, III- 130, III-131, IV-15, IV-16, IV-17, IV-20, IV-25, IV-26, IV-30, IV-34, V-3, and IX-47. The following compounds were shown to have K± values between 0.1 and 1.0 pM for GSK-3: compounds II- 103, II-104, II-35, II-44, II-45, II-49, II-50, II-97, II-101, II--22, II-32, III-41, III-43, III-44, III-28, III-50, III-29, III-64, III-71, III-74, IIJ-78, IJI-82, III-88, III-90, III-102, III-105, III-:i07, III-II0, III- II2, III-II4, III-II5, III-122, III-124, IXI-124, IV-1, III-l, III-138, III-140, III-142, III-129, III-132, III- 134, III-135, III-136, IV-1, IV-10, IV-II, IV-12, IV-13, IV-14, IV-19, IV-21, IV-22, IV-23, IV-24, IV-3, IV-4, IV- 6, IV-7, IV-8, IV-29, IV-31, IV-32, IV-33, IV-36, V-2, V- 7, IX-38, IX-154, and IX-177. The following compounds were shown to have K± values between 1.0 and 20 \|iM for GSK-3: compounds II-43, II-65, II-48, II-47, II-51, II-68, II-52, II-72, II-100, II-98, II-89, III-68, III-81, III-83, III-91, . III-94, III-95, III-96, III-97, III-98, III-99, III-100, III-101, III-103, III-123, III-137, III-139, III-143, III-145, III-146, V-4, V-8, IX-156, and IX-176. BIOLOGICAL TESTING EXAMPLE 2 KI DETERMINATION FOR INHIBITION OF AURORA-2. Compounds were screened in the following manner for their ability to inhibit Aurora-2 vising a standard coupled enzyme assay (Pox et al (1998) protein Sci 7, 2249). To an assay stock buffer solution containing 0.1M HEPES 7.5, 10 mM MgCl2, 1 mM DTT, 25 mM NaCl, 2.5 mM phosphoenolpyruvate, 300 tnM NADH, 30 mg/ml pyruvate kinase, 10 mg/ml lactate dehydrogenase, 40 mM ATP, and 800 fM peptide (LKRASLG, American Peptide, Sunnyvale, CA) was added a DMSO solution of a compound of the present invention to a final concentration of 3 0 JIM. The resulting mixture was incubated at 30 C for 10 min. The reaction was initiated by the addition of 10 /xL of Aurora-2 stock solution to give a final concentration of 70 nM in the assay. The rates of reaction were obtained by monitoring absorbance at'340 nm over a 5 minute read time at 30 °C using a BioRad Ultramark plate reader • (Hercules, CA) . The Ki values were determined from the rate data as a function of inhibitor concentration. The following compounds were shown to have Ki values less than 0.1 \|jM for Aurora-2: compounds II-33, II-34, II-36, II-37, II-40, II-41, II-55, III-7, III-9, III-37, III-38, III-39, III-40, III-41, III-42, III-44, III-45, 222-46, III-47, 221-48, III-49, III-50, III-51, III-52, III-53, 222-54, III-55, III-56, III-57, III-59, III-60, II2-61, III-63, III-30, III-65, III-66, III-67, III-70, II2-31, 121-76, 222-77, 222-78, 212-80, 222-32, 222-33, 222-34, 222-106, 122-108, 221-109, II2-II0, 222- III, II2-II2, III-II4, 122-35, 222-II5, III-II6, 122-II7, 222-II8, 121-II9, III-120,-222-121, 2V-7, 2V-30, 2V-32, and 2V-34. The following compounds were shown to have KA values between 0.1 and 1.0 jiM for Aurora-2: compounds 22- 1, 22-105, 21-35, 22-38, 22-39, 22-42, 21-64, 22-70, 22- 53, 22-99, 21-77, 22-79, 22-86, 22-20, 21-93, 22-94, 222- 28, 122-58, 222-64, 221-71, III-73, III-74, III-75, 222- 102, III-105, III-107, III-II3, III-124, III-l, III-130, IV-1, IV-3, IV-4, IV-6, IV-29, IV-33, and V-4. The following compounds were shown to have Ki values between 1.0 and 20 fiM for Aurora-2: compounds II- 103, II-104., II-57, II-59, II-61, II-63/ II-67, II-69, II-75, II-76, II-10, II-19, II-78, II-54, II-80, II-.82, II-21, II-90, II-91, II-96, II-107, III-68, III-79, III- 82, III-101, III-103, III-127, III-141, III-129, III-132, IV-31, V-2, IX-47, IX-154, and IX-177. BIOLOGICAL TESTING EXAMPLE 3 CDR-2 INHIBITION ASSAY ' Compounds were screened in the following manner for their ability to inhibit CDK-2 using a standard coupled enzyme assay (Fox et al (1998) Protein Scl 7, 2249). To an assay stock buffer solution containing 0.1M HEPES 7.5, 10 mM MgCl2, 1 mM DTT, 25 mM NaCl, 2.5 mM phosphoenolpyruvate, 300 mM NADH, 30 mg/ml pyruvate kinase, 10 mg/ml lactate dehydrogenase, 100 mM ATP, and 100 /zM peptide (MAHHHRSPRKRAKKK, American Peptide, Sunnyvale, CA) was added a DMSO solution of a compound of the present invention to a final concentration of 30 /xM. The resulting mixture was incubated at 30 °C for 10 min. The reaction was initiated by the addition of 10 /iL of CDK-2/Cyclin A stock solution to give a final concentration of 25 nM in the assay. The rates of reaction were obtained by monitoring absorbance at 340 nm over a 5-minute read time at 30 °C using a BioRad Ultramark plate reader (Hercules, CA) . The Ki values were determined from the rate data as a function of inhibitor concentration. BIOLOGICAL TESTING EXAMPLE 4 ERK INHIBITION ASSAY Compounds were assayed for the inhibition of KRK2 by a spectrophotometric coupled-enzyme assay (Fox et al (1998) Protein Sci 7, 2249). In this assay, a fixed concentration of activated ERK2 (10 nM) was incubated with various concentrations of the compound in DMSO (2.5 %) for 10 min. at 30°C in 0.1 M HEPES buffer, pH 7.5, containing 10 mM MgCl2, 2.5 mM phosphoenolpyruvate, 200 ?M NADH, 150 ?g/mL pyruvate kinase, 50 ?g/mL lactate dehydrogenase, and 200 fM erktide peptide. The reaction was initiated by the addition of 65 jzM ATP. The rate of decrease of absorbance at 340 nM was monitored. The ICS0 was evaluated from the rate data as a function of inhibitor concentration. The following compounds were shown to have a Ki value of II7, III-II8, III-120, and IV-4. ' The following compounds were shown to have a Ki value of between lyM and 12pM for ERK-2: III-63, III-40, and III-108. BIOLOGICAL TESTING EXAMPLE 5 AKT INHIBITION ASSAY Compounds were screened for their ability to inhibit AKT using a standard coupled enzyme assay (Fox et al., Protein Sci., (1998) 7, 2249). Assays were carried out in a mixture of 100 mM HEPES 7.5, 10 mM MgC12, 25 mM NaCl , 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 170 fM. ATP (Sigma Chemicals) and "200 fM peptide (RPRAATF, American Peptide, Sunnyvale, CA) . Assays were carried out at 3-0 . C and 45 nM AKT. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 /iM NADH, 30 /ig/ML pyruvate kinase and 10 fig /ml lactate dehydrogenase. An assay stock buffer solution was prepared containing all of the reagents listed above, with the exception of AKT, DTT, and the test compound of interest. 56 jil of the- stock solution was placed in a 384 well plate followed by addition of 1 jil of 2 mM DMSO stock containing the test compound {final compound concentration 3 0 /zM) . The plate was preincubated for about 10 minutes at 30 C and the reaction initiated by addition of 10 fil of enzyme (final concentration 45 nM) and 1 mM DTT.- Rates of reaction were obtained using a BioRad Ultramark plate reader (Hercules, CA) over a 5- minute read time at 3 0 C. Compounds showing greater than 50% inhibition versus standard wells containing the assay mixture and DMSO without test compound were titrated to determine IC50 values. BIOLOGICAL TESTING EXAMPLE 6 SRC INHIBITION ASSAY The compounds were evaluated as inhibitors of human Src kinase using either a radioactivity-based assay or spectrophotometric assay. Src Tin^1'1'!"'? -?Pn Agsay A: Radioactivity-based Assay The compounds were assayed as inhibitors of full length recombinant human Src kinase (from Upstate Biotechnology, cat. no. 14-II7) expressed and purified from baculo viral cells. Src kinase activity was monitored by following the incorporation of 33P from ATP into the tyrosine of a random poly Glu-Tyr polymer substrate of composition, GlurTyr =4:1 (Sigma, cat. no. P-0275) . The following were the final concentrations of the assay components: 0.05 M HEPES, pH 7.6, 10 mM MgCl2, 2 mM DTT, 0.25 mg/ml BSA, 10 (iM ATP (1-2 fiC± 33P-ATP per reaction) , 5 mg/ml poly Glu-Tyr, and 1-2 units of recombinant human Src kinase. In a typical assay, all the reaction components with the exception of ATP were pre-mixed and aliquoted into assay plate wells. Inhibitors dissolved in DMSO were added to the wells to give a final DMSO concentration of 2.5%. The assay plate was incubated at 30 °C for 10 min before initiating the reaction with 3JP-ATP. After 20 min of- reaction, the reactions were quenched with 150 fil of 10% trichloroacetic acid (TCA) containing 20 mM Na3PO4. The quenched samples were then transferred to a 96-well filter plate (Whatman, UNI-Filter GF/F Glass Fiber Filter, cat no. 7700-3310) installed on a filter plate .vacuum manifold. Filter plates were washed four.times with 10% TCA containing 20 mM Na3PO4 and then 4 times with methanol. 200/tl of scintillation fluid was then added to each well. The plates were sealed and the amount of radioactivity associated with the filters was quantified on a TopCount scintillation counter. The radioactivity incorporated was plotted as a function of the inhibitor concentration. The data was fitted to a competitive inhibition kinetics model to get the K± for the compound. Src Inhibition Assay B; Spectrophotometric Assay The ADP produced from ATP by the human recombinant Src kinase-catalyzed phosphorylation of poly Glu-Tyr substrate was quanitified using a coupled enzyme assay (Fox et al (1998) Protein Sex 7, 2249). In this assay one molecule of NADH is oxidised to NAD for every molecule of ADP produced in the kinase reaction. The disappearance of NADH can be conveniently followed at 340 nm. The following were the final concentrations of the assay components: 0.025 M HEPES, pH 7.6, 10 mM MgCl2, 2 mM DTT, 0.25 mg/ml poly Glu-Tyr, and 25 nM of recombinant human Src kinase. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 200 ?M NADH, 30 Kg/ml pyruvate kinase and 10 jig/ml lactate dehydrogenase. In a typical assay, all the reaction components with the exception of ATP were pre-mixed and aliquoted into assay plate wells. Inhibitors dissolved in DMSO were added to the wells to give a filial DMSO' concentration of 2.5%. The assay plate was incubated at 30 C for 10 tnin before initiating the reaction with 100 juM ATP. The absorbance change at 340 nm with time, the rate of the reaction, was monitored on a molecular devices plate reader. The data of rate as a function of the inhibitor concentration was fitted to compettive inhibition kinetics model to get the KA for the compound. The following compounds were shown to have a Ki value of .III-35, III-47, III-65, III-66, III-37, III-38,III-39, III-40, III-42, III-44, III-48,. III-49, III-70, III-45, III-78, III-76, and IV- 32. The following compounds were shown to have a Ki value of between lOOnM and lyM for SRC: III-63, III-71, III-75, III-73, III-72, III-74, III-80, III-50, IV-30. The following compounds were shown to have a K± value of between 1^ and 6fiM for SRC: III-79, IV-1, and IV-31. While we have hereinbefore presented a number of embodiments of this invention, it is apparent that our basic construction can be altered to provide other embodiments which utilize the compounds and methods of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the appended claims rather than by the specific embodiments which have been represented by way of example. WE CLAIM: 1. A compound of formula II: or a pharmaceutically acceptable derivative or prodrug thereof, wherein; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from -R1, any substitutable non- ortho carbon position on Ring C is independently substituted by -R5, and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or -R8; R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or -R8, said C1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is substituted by oxo or T-R3, and any substitutable nitrogen on said ring formed by Rx and RY is substituted by R4; T is a valence bond or a C1-4 alkylidene chain; R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -NO?, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -NO2, -CN, -S(O)R, -S(O)2R, -SR, -N (R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7) CO2(d-6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N (R7)CON(R7)2, -N(R7)SO2N(R7)2, -N(R4)SO2R, or -0C(=O)N(R7) 2! each R is independently selected from hydrogen or an optionally substituted group selected from C!-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; each R5 is independently selected from -R, halo, -OR, -C (=O)R, -CO2R, -COCOR, -NO2, -CN, -S (O) R, -SO2R, -SR, -N (R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) CO2 (optionally substituted Ci-6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2,' -C=N-OR, -N(R4)CON(R4)2, -N (R4) SO2N (R4) 2, -N (R4)SO2R, or -OC (=O)N(R4)2, or R5 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C; V is -0-, -S-, -SO-, -S02-, -N(R6)SO2-, -SO2N(R6)-, -N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N(R6)C(O)O-, -N (R6) CON (R6) -, -N (R6)SO2N(R6)-, -N(R6)N(R6)-, -C(O)N(R6)-, -0C (0) N (R6)-, -C (R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N (R6)-, -C(R6)2N(R6)-, -C(R6)2N(R6)C(O)-, -C (R6) 2N (R6) C (0) 0-, -C(R6)=NN(R5)-, -C(R6)=N-O-, -C (R6) 2N (R6) N (R6)-, -C (R6)2N(R6)SO2N(R6)-/ or -C (R6) 2N (R6) CON (R6)-; W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6) 2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -C02-, -C (R6) OC (0) -, -C (R6)OC(O)N(R6)-, -C(R6)2N(R6)CO-, -C (R6) 2N (R6) C (0) 0-,' -C (R6)=NN(R6)-, -C(R6)==N-O-, -C (R6) 2N (R6) N (R6)-, -C(R6)2N(R6) SO2N(R6)-, -C(R6)2N(R6)CON(R6)-, or -CON(R6)-; each R6 is independently selected from hydrogen, or an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; each R7 is independently selected from hydrogen or an optionally substituted Ci-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; and each R9 is independently selected from an optionally substituted C1-4 aliphatic group, -OR6, -SR6, -COR6, -SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or -CO2R6. 2. The compound as claimed in claim 1, wherein said compound has one or more features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from an optionally substituted naphthyl, quinolinyl or isoquinolinyl ring; (b) Rx is hydrogen or C1-4 aliphatic and Ry is T-R3, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted 5-7 membered unsaturated or partially unsaturated ring having 0-2 ring nitrogens; (c) R1 is -halo, an optionally substituted C1-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; and (d) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a Ci-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring. 3. The compound as claimed in claim 2, wherein: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from an optionally substituted naphthyl, quinolinyl or isoquinolinyl ring; (b) Rx is hydrogen or C1-4 aliphatic and Ry is T-R3, or Rx and Ry are taken together with their intervening atoms to form an optionally substituted 5-7 membered unsaturated or partially unsaturated ring having 0-2 ring nitrogens; (c) R1 is -halo, an optionally substituted C1-6 aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R5, -SO2NH2, -N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; and (d) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, heteroaryl, or a C1-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a (b) substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring. 4. The compound as claimed in claim 2, wherein said compound has one or more features selected from the group consisting of: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from an optionally substituted naphthyl ring; (b) Rx is hydrogen or methyl and Ry is -R, N(R4) 2, or -OR, or Rx and Ry are taken together with their intervening atoms to form a 5-7 membered unsaturated or partially unsaturated carbocyclo ring optionally substituted with -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4) 2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted Ci- 6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N(R4)CON (R4)2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -0C (=0) N (R4) 2, ; (c) R1 is -halo, a Ci-6 haloaliphatic group, a C1-6 aliphatic group, phenyl, or -CN; (d) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, or a Ci-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and (e) each R5 is independently selected from -halo, -CN, -N02, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4)SO2R. 5. The compound as claimed in claim 4, wherein: (a) Ring C is a phenyl or pyridinyl ring, optionally substituted by -R5, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from an optionally substituted naphthyl ring; (b) R- is hydrogen or methyl and Ry is -R, N(R^) 2, or -OR, or Rx and Ry are taken together with their intervening atoms to form a 5-7 membered unsaturated or partially unsaturated carbocyclo ring optionally substituted with -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4) 2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted Ci- 6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N(R4)CON (R4)2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -0C (=0) N (R4) 2, ; (c) R1 is -halo, a C1-6 haloaliphatic group, a Ci-6 aliphatic group, phenyl, or -CN; (d) R2' is hydrogen and R2 is hydrogen or a substituted or unsubstituted group selected from aryl, or a C1-6 aliphatic group, or R2 and R2' are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and (e) each R5 is independently selected from -halo, -CN, -N02, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4)SO2R. 6. The compound as claimed in claim 4, wherein said compound has one or more features selected from the group consisting of: (a) Rx is hydrogen or methyl and Ry is methyl, methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or an optionally substituted group selected from 2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry are taken together with their intervening atoms to form a 6-membered unsaturated or partially unsaturated carbocyclo ring optionally substituted with -halo, -R, -OR, -COR, -CO2R, -CON(R4)2/ -CN, or -N(R4)2 wherein R is an optionally substituted C1-6 aliphatic group; (b) R1 is -halo, a C1-4 aliphatic group optionally substituted with halogen, or -CN; (c) R- ana R-' are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -C1- 4 haloalkyl, -N02, -0 (C1-4 alkyl) , -C02 (C1-4 alkyl) , -CN, -S02 (C1-4 alkyl), -SO2NH2, -0C(0)NH2/ -NH2SO2 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl), -C(0)NH2, or -CO (d-4 alkyl), wherein the (C1-4 alkyl) is a straight, branched, or cyclic alkyl group; and (d) each R5 is independently selected from -Cl, -F, -CN, -CF3, -NH2, -NH(Ci-4 aliphatic), -N(d-4 aliphatic) 2, -0(C1-4 aliphatic), Ci-4 aliphatic, and -CO2(Ci_j aliphatic) . 7. The compound as claimed in claim 6, wherein: (a) Rx is hydrogen or methyl and Ry. is methyl, methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or an optionally substituted group selected from 2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry are taken together with their intervening atoms to form a benzo ring or a partially unsaturated carbocyclo ring optionally substituted with -halo, -R, -OR, -COR, -CO2R, -CON(R4)2/ -CN, or -N(R4)2 wherein R is an optionally substituted d_6 aliphatic group; (b) R1 is -halo, a C1-4 aliphatic group optionally substituted with halogen, or -CN; (c) R2 and R2' are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -Ci_ 4 haloalkyl, -N02, -0 (d-4 alkyl) , -C02 (d-4 alkyl) , -CN, -S02 (d-4 alkyl), -SO2NH2, -OC(O)NH2, -NH2SO2 (d-4 alkyl) , -NHC(O) (C1-4 alkyl), -C(0)NH2, or -CO (C1-4 alkyl) , wherein the (d-4 alkyl) is a straight, branched, or cyclic alkyl group; and (a) (d) each R5 is independently selected from -Cl, -F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic) i, -O(C1-4 aliphatic), C1-4 aliphatic, and -CO2(C1-4 aliphatic). 8. The compound as claimed in claim 7, wherein Rx and Ry are each methyl or R and Ry are taken together with the pyrimidine ring to form an optionally substituted ring selected from quinazoline or tetrahydroquinazoline, and R2 and R2' are taken together with the pyrazole ring to form an optionally substituted indazole ring. 9. The compound as claimed in claim 1, wherein said compound is selected from Table 1. 10. A composition comprising a compound as claimed in any one of claims 1-9 and a pharmaceutically acceptable carrier such as herein described. II. The composition as claimed in claim 10, having a second therapeutic agent, such as herein described. 12. A pharmaceutical composition as claimed in claim 10, which is capable of being used for treating diabetes, Alzheimer's disease, Huntington's Disease, Parkinson's Disease, AIDS-associated dementia, amyotrophic lateral sclerosis (AML), multiple sclerosis (MS), schizophrenia, cardiomycete hypertrophy, reperfusion/ischemia, baldness, or a cancer selected from breast, ovary, cervix, prostate, testis, genitourinary tract, esophagus, larynx, glioblastoma, neuroblastoma, stomach, skin, keratoacanthoma, lung, epidermoid carcinoma, large cell carcinoma, small cell carcinoma, lung adenocarcinoma, bone, colon, adenoma, pancreas, adenocarcinoma, thyroid, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, sarcoma, bladder carcinoma, liver carcinoma and biliary passages, kidney carcinoma, myeloid disorders, lymphoid disorders, Hodgkin's, hairy cells, buccal cavity and pharynx (oral), lip, tongue, mouth, pharynx, small intestine, colon-rectum, large intestine, rectum, brain and central nervous system, and leukemia. 13. A method of inhibiting GSK-3 or Aurora activity in a biological sample comprising contacting said biological with the compound as claimed in claim 1. 14. A pharmaceutical composition as claimed in claim 10, which is capable of being used for treating diabetes, Alzheimer's disease, Huntington's Disease, Parkinson's Disease, AIDS-associated dementia, amyotrophic lateral sclerosis (AML), multiple sclerosis (MS), schizophrenia, cardiomycete hypertrophy, reperfusion/ischemia, and baldness. 15. The pharmaceutical composition as claimed in claim 14, which has a second therapeutic agent, such as herein described. 16. The pharmaceutical composition as claimed in claim 14, wherein said disease is diabetes. 17. The pharmaceutical composition as claimed in claim 14, wherein said disease is Alzheimer's disease. 18. The pharmaceutical composition as claimed in claim 14, wherein said disease is schizophrenia. 19. The pharmaceutical composition as claimed in claim 10, which is capable of being used for enhancing glycogen synthesis in a patient in need thereof. 20. The pharmaceutical composition as claimed in claim 10, which is capable of being used for lowering blood levels of glucose in a patient in need thereof. 21. The pharmaceutical composition as claimed in claim 10, which is capable of being used for inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof. 22. The pharmaceutical composition as claimed in claim 10, which is capable of being used for inhibiting the phosphorylation of (5-catenin in a patient in need thereof. 23. A pharmaceutical composition as claimed in claim 10, which is capable of being used for treating a cancer selected from breast, ovary, cervix, prostate, testis, genitourinary tract, esophagus, larynx, glioblastoma, neuroblastoma, stomach, skin, keratoacanthoma, lung, epidermoid carcinoma, large cell carcinoma, small cell carcinoma, lung adenocarcinoma, bone, colon, adenoma, pancreas, adenocarcinoma, thyroid, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, sarcoma, bladder carcinoma, liver carcinoma and biliary passages, kidney carcinoma, myeloid disorders, lymphoid disorders, Hodgkin's, hairy cells, buccal cavity and pharynx (oral), lip, tongue, mouth, pharynx, small intestine, colon- rectum, large intestine, rectum, brain and central nervous system, and leukemia. 24. The pharmaceutical composition as claimed in claim 23, which has a second therapeutic agent, such as herein described. 25. The pharmaceutical composition as claimed in claim 23, wherein said disease is melanoma or is selected from colon, lung, stomach, or breast cancer. 26. A compound of formula A: 23. wherein: R1 is selected from CF3; R5 is one to three substituents that are each independently selected from H, Cl, F, CF3, N02, or CN, provided that R1 and Rs are not simultaneously Cl; Rx and Rv are independently selected from T-R3, or Rx and RY are taken together with their intervening atoms to form, a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by R* and Ry is optionally and independently substituted by T-R3, and any substitutable nitrogen on said ring formed by Rx and Ry is substituted by R4; T is a valence bond or a d-4 alkylidene chain; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -N02, -CN, -S (O) R, -S(O)2R, -SR, -N (R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7) CO2 (optionally substituted C1-6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N(R7)CON(R7)2/ -N (R7) SO2N (R7) 2, -N (R4)SO2R, or -OC(=O)N(R7)2; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6_i0 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; and each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring. wherein: R2 and R2' are independently selected from -R, -T-W-R6, or R2 and R2' are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R2 and R2' is substituted by halo, oxo, -CN, -N02, -R7, or -V-R6, and any substitutable nitrogen on said ring formed by R2 and R2' is substituted by R4; Rx and Ry are independently selected from T-R~, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is optionally and independently substituted by T-R3, and any'substitutable nitrogen on said ring formed by Rx and Ry is substituted by R4; T is a valence bond or a C1-4 alkylidene chain; V is -O-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(R6)-, -N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N(R6)C(O)0-, -N (R6) CON (R6) -, -N (R6)SO2N(R6)-, -N(R6)N(R6)-, -C(O)N(R6)-, -OC (O) N (R6) -, -C (R6)2O-, -C(R6}2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N (R6)-, -C(R6)2N(R6)-, -C(R6)2N(R6)C(O)-, -C (R6) 2N (R6) C (O) O-, -C(R6)=NN(R6)-, -C(R6)=N-O-, -C (R6) 2N (R6) N (R6)-, -C (R6)2N(R6)SO2N(R6)-, or -C (R6) 2N (R6) CON (R6) -; W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6) 2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-, -C (R6) OC (0)-, -C (R6)OC(O)N(R6)-, -C(R6)2N(R6)CO-, -C (R6) 2N (R6) C (0) 0-, -C (R6)=NN(R6)-, -C(R6)=N-O-, -C (R6) 2N (R6) N (R6)-, -C(R6)2N(R6) SO2N(R6)-, -C(R6)2N(R6)CON(R6)-, or -CON(R6)-; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -N02, -CN, -S(O)R, -S(O)2R, -SR, -N (R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)C0R, -N(R7) C02 (optionally substituted d-6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N(R7)CON(R7)2, -N (R7) SO2N (R7) 2, -N (R4)SO2R, or -OC(=O)N(R7)2; each R is independently selected from hydrogen or an optionally substituted group selected from Ci-6 aliphatic, C6-io aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring. each R' is independently selected from hydrogen or an optionally substituted C1-4 aliphatic group, or two R6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring; and each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the: same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring with the proviso that R2 is other than t-butyl and R2 is other than methyl when Rx is Br, Ry is H, R2' is H. 29. The compound as claimed in claim 28, wherein Rx and Ry are each methyl, or Rx and Ry are taken together with the pyrimidine ring to form a quinazoline or tetrahydroquinazoline ring. 30. The compound as claimed in claim 29, wherein R2 and R2' are taken together with the pyrazole ring to form an indazole ring. wherein: Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 0-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by Rx and Ry is optionally and independently substituted by T-R3, and any substitutable nitrogen on said ring formed by is substituted by R4; T is a valence bond or a C1-4 alkylidene chain; R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R, -COCOR, -COCH2COR, -N02, -CN, -S(O)R, -S(O)2R, -SR, -N (R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7) CO2 (optionally substituted C1-6 aliphatic) , -N (R4) N (R4) 2, -C==NN(R4)2, -C=N-OR, -N(R7)CON(R7)2, -N (R7) SO2N (R7) 2, -N (R4)SO2R, or -OC(=O)N(R7)2; each R is independently selected from hydrogen or an optionally substituted group selected from C1-6 aliphatic, C6-io aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; each R4 is independently selected from -R7, -COR7, -CO2 (optionally substituted C^ aliphatic) , -CON(R7)2, or -SO2R7, or two R4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring; and each R5 is independently selected from -R, halo, -OR, -C (=O)R, -CO2R, -COCOR, -NO2, -CN, -S (0) R, -SO2R, -SR, -N (R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) CO2 (optionally substituted Ci-6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N (R4) SO2N (R4) 2, -N (R4)SO2R, or -OC(=O)N(R4)2 each R7 is independently selected from hydrogen or an optionally substituted Ci-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring. 32. The compound as claimed in claim 31, wherein Rx and Ry are each methyl, or Rx and Ry are taken together with the pyrimidine ring to form a quinazoline or tetrahydroquinazoline ring. This invention describes novel pyrazole compounds of formula II: wherein Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1, 2, 4-triazinyl ring, and R2, R2, Rx, and Ry are as described in the specification. Ring C has an ortho substituent and is optionally substituted in the non-ortho positions. R2 and R2 are optionally taken together with their intervening atoms to form a fused ring system, such as an indazole ring; and Rx and Ry are optionally taken together with their intervening atoms to form a fused ring system, such as a quinazoline ring. The compounds are useful as protein kinase inhibitors, especially as

Full Text

PYRAZOLE COMPOUNDS USEFUL AS PROTEIN KINASE INHIBITORS
CROSS REFERENCE TO REIATED APPLICATIONS
This application claims priority to US
Provisional Patent Application 60/232,795 filed September
15, 2000, US Provisional Patent Application 60/257,887
filed December 21, 2000 and US Provisional Patent
Application 60/286,949 filed April 27, 2001, the contents
of which are incorporated herein by reference.
FIELD OF THE INVENTION
The present invention is in the field of
medicinal chemistry and relates to compounds that are
protein kinase inhibitors, compositions containing such
compounds and methods of use. ore particularly, this
invention relates to compounds that are inhibitors of
GSK-3 and Aurora-2 protein kinases. The invention also
relates to methods of treating diseases associated with
these protein kinases, such as diabetes, cancer and
Alzheimer's disease.
BACKGROUND OF THE INVENTION
The search for new therapeutic agents has been
greatly aided in recent years by better understanding of
the structure of enzymes and other biomolecules
associated with target diseases. One important class of
enzymes that has been the subject of extensive study is
the protein kinases.
Protein kinases mediate intracellular signal
transduction. They do this by effecting a phosphoryl
transfer from a nucleoside triphosphate to a protein
acceptor that is involved in a signaling pathway. There

are a number of kinases and pathways through which
extracellular and other stimuli cause a variety of
cellular responses to occur inside the cell. Examples of
such stimuli include environmental and chemical stress
signals (e.g. osmotic shock, heat shock, ultraviolet
radiation, bacterial endotoxin, H2O2), cytokines (e.g.
interleukin-1 (IL-l) and tumor necrosis factor a (TNF-
?)) , and growth factors (e.g. granulocyte macrophage-
colony-stimulating factor (GM-CSF), and fibroblast growth
factor (FGF). An extracellular stimulus may effect one
or more cellular responses related to cell growth,
migration, differentiation, secretion of hormones,
activation of transcription factors, muscle contraction,
glucose metabolism, control of protein synthesis and
regulation of cell cycle.
Many diseases are associated with abnormal
cellular responses triggered by protein kinase-mediated
events. These diseases include autoimmune diseases,
inflammatory diseases, neurological and neurodegenerative
diseases, cancer, cardiovascular diseases, allergies and
asthma, Alzheimer's disease or hormone-related diseases.
Accordingly, there has been a substantial effort in
medicinal chemistry to find protein kinase inhibitors
that are effective as therapeutic agents.
Aurora-2 is a serine/threonine protein kinase
that has been implicated in human cancer, such as colon,
breast and other solid tumors. This kinase is believed
to be involved in protein phosphorylation events that
regulate the cell cycle. Specifically, Aurora-2 may play
a role in controlling the accurate segregation of
chromosomes during mitosis. Misregulation of the cell
cycle can lead to cellular proliferation and other
abnormalities. In human colon cancer tissue, the aurora-

2 protein has been found to be overexpressed. See
Bischoff et al., EMBO J., 1998, 17, 3052-3065; Schumacher
et al., J. Cell Biol., 1998, 143, 1635-1646; Kimura et
al., J. Biol. Chem., 1997, 272, 13766-13771.
Glycogen synthase kinase-3 (GSK-3) is a
serine/threonine protein kinase comprised of a and p
isoforms that are each encoded by distinct genes [Coghlan
et al., Chemistry & Biology, 7, 793-803 (2000); Kim and
Kimmel, Curr. Opinion Genetics Dev., 10, 508-514 (2000)].
GSK-3 has been implicated in various diseases including
diabetes, Alzheimer's disease, CNS disorders such as
manic depressive disorder and neurodegenerative diseases,
and cardiomyocete hypertrophy [WO 99/65897; WO 00/38675;
and Haq et al., J. Cell Biol. (2000) 151, 117]. These
diseases may be caused by, or result in, the abnormal
operation of certain cell signaling pathways in which
GSK-3 plays a role. GSK-3 has been found to
phosphorylate and modulate the activity of a number of
regulatory proteins. These proteins include glycogen
synthase which is the rate limiting enzyme necessary for
glycogen synthesis, the microtubule associated protein
Tau, the gene transcription factor p-catenin, the
translation initiation factor elF2B, as well as ATP
citrate lyase, axin, .heat shock factor-1, c-Jun, c-Myc,
c-Myb, CREB, and CEPBa. These diverse protein targets
implicate GSK-3 in many aspects of cellular metabolism,
proliferation, differentiation and development.
In a GSK-3 mediated pathway that is relevant
for the treatment of type II diabetes, insulin-induced
signaling leads to cellular glucose uptake and glycogen
synthesis. Along this pathway, GSK-3 is a negative
regulator of the insulin-induced signal. Normally, the
presence of insulin causes inhibition of GSK-3 mediated

phosphorylation and deactivation of glycogen synthase.
The inhibition of GSK-3 leads to increased glycogen
synthesis and glucose uptake [Klein et al., PNAS, 93,
8455-9 (1996); Cross et al., Biochem. J., 303, 21-26
(1994); Cohen, Biochem. Soc. Trans., 21, 555-567 (1993);
Massillon et al., Biochem J. 299, 123-128 (1994)].
However, in a diabetic patient where the insulin response
is impaired, glycogen synthesis and glucose uptake fail
to increase despite the presence of relatively high blood
levels of insulin. This leads to abnormally high blood
levels of glucose with acute and long term effects that
may ultimately result in cardiovascular disease, renal
failure and blindness. In such patients, the normal
insulin-induced inhibition of GSK-3 fails to occur. It
has also been reported that in patients with type II
diabetes, GSK-3 is overexpressed [WO 00/38675].
Therapeutic inhibitors of GSK-3 are therefore potentially
useful for treating diabetic patients suffering from an
impaired response to insulin.
GSK-3 activity has also been associated, with
Alzheimer's disease. This disease is characterized by
the well-known ?-amyloid peptide and the formation of
intracellular neurofibrillary tangles. The
neurofibrillary tangles contain hyperphosphorylated Tau
protein where Tau is phosphorylated on abnormal sites.
GSK-3 has been shown to phosphorylate these abnormal
sites in cell and animal models. Furthermore, inhibition
of GSK-3 has been shown to prevent hyperphosphorylation
of Tau in cells [Lovestone et al., Current Biology 4,
1077-86 (1994); Brownlees et al., Neuroreport 8, 3251-55
(1997)]. Therefore, it is believed that GSK-3 activity
may promote generation of the neurofibrillary tangles and
the progression of Alzheimer's disease.

Another substrate of GSK-3 is ?-catenin which
is degradated after phosphorylation by GSK-3. Reduced
levels of ?-catenin have been reported in schizophrenic
patients and have also been associated with other
diseases related to increase in neuronal cell death
[Zhong et al., Nature, 395, 698-702 (1998); Takashima et
al., PNAS, 90, 7789-93 (1993); Pei et al., J.
Neuropathoi. Exp, 56, 70-78 (1997)].
As a result of the biological importance of
GSK-3, there is current interest in therapeutically
effective GSK-3 inhbitors. Small molecules that inhibit
GSK-3 have recently been reported [WO 99/65897 (Chiron)
and WO 00/38675 (SmithKline Beecham)].
For many of the aforementioned diseases
associated with abnormal GSK-3 activity, other protein
kinases have also been targeted for treating the same
diseases. However, the various protein kinases often act
through different biological pathways. For example,
certain quinazoline derivatives have been reported
recently as inhibitors of p38 kinase (WO 00/12497 to
Scios). The compounds are reported to be useful for
treating conditions characterized by enhanced p38-?
activity and/or enhanced TGF-p activity. While p38
activity has been implicated in a wide variety of
diseases, including diabetes, p38 kinase is not reported
to be a constituent of an insulin signaling pathway that
regulates glycogen synthesis or glucose uptake.
Therefore, unlike GSK-3, p38 inhibition would not be
expected to enhance glycogen synthesis and/or glucose
uptake.
There is a continued need to find new
therapeutic agents to treat human diseases. The protein
kinases aurora-2 and GSK-3 are especially attractive

targets for the discovery of new therapeutics due to
their important role in cancer, diabetes, Alzheimer's
disease and other diseases.
DESCRIPTION OF THE INVENTION
It has now been found that compounds of this
invention and pharmaceutical compositions thereof are
effective as protein kinase inhibitors, particularly as
inhibitors of aurora-2 and GSK-3. These compounds have
the general formula I:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
Z1 to Z4 are as described below;
Ring A is selected from the group consisting of:

G is Ring C or Ring D;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8;
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-member ed aryl or
heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;
R1 is selected from -halo, -CN, -N02, T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered.heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,

and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R8, said C1-6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or R1
and an adj acent substituent taken together with their
intervening atoms form said ring fused to Ring C;
Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
substituted by oxo or T-R3, and any substitutable
nitrogen on said ring formed by Rx and Ry is
substituted by R4;
T is a valence bond or a C1-4 alkylidene chain;
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -N02, -CN, -S(O)R, -S(O)2R, "SR,
-N(R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR,
-N(R-7)CO2 (optionally substituted Ci-6 aliphatic),
-N(R4)N(R4)2f -C=NN(R4)2, -C=N-OR, -N (R7) CON(R7) 2,
-N(R7)SO2N(R7)2, -N(R4)SO2R, or -OC (=O)N(R7) 2;
each R is independently selected from hydrogen or an
optionally substituted group selected from C3.-6

aliphatic, C6-io aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7, -CO2(Ci-e
aliphatic), -CON(R7)2, or -SO2R7; or two R4 on the same
nitrogen are taken together to form a 5-8 membered
heterocyclyl or heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -NO2/ -CN, -S(O)R, -SO2R, -SR,
-N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR,
-N(R4) CO2(optionally substituted C1_6 aliphatic) ,
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R4) CON(R4) 2,
-N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC (=O)N(R4) 2, or R5 and
an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
V is -O-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(R6)-,
-N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N(R6)C(O)O-,
-N(R6)CON(Re)-, -N(R6)SO2N(Re)-, -N(R6)N (R6) -,
-C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(R6)2S-,
-C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C (R6)2N(R6) -,
-C(R6)2N -C(Re)=N-O-, -C(R6)2N(R6)N(R6)-, -C (R6) 2N (R6) SO2N(Re) - , or
-C (R6) 2N(R6) CON(R6) - ;
W is -C(R6)2O-, -C{R6)2S-, -C{R6)2SO-, -C(Re)2SO2-,
-C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-,
-C(R6)OC(0)-, -C(R6)OC(O)N(R6)-, -C(R6) 2N(R6) CO- ,
-C(R6)2N(R6)C(0)0-, -C(Rs)=NN(R6)-, -C(R6)=N-O-,
-C(R6)2N(Re)N(R6)-, -C(R6)2N(R6)SO2N(R6)-,
-C(R6)2N(R6)C0N(R6)-, or -CON(R6)-;
each R6 is independently selected from hydrogen or an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together

with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1_6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R8 is independently selected from an optionally
substituted C1-4 aliphatic group, -OR6, -SR6, -COR6,
-SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or
-CO2R6; and
R9 is selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR,
-NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2/
-SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) CO2 (optionally
substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=MN(R4)2f
-C=N-OR, -N(R4)CON(R4)2, -N (R4) SO2N(R4) 2, -N(R4)S02R, or
-OC(=O)N(R4)2..
As used herein, the following definitions shall
apply unless otherwise indicated. The"phrase "optionally
substituted" is used interchangeably with the phrase
"substituted or unsubstituted" or with the term
* (un> substituted." Unless otherwise indicated, an
optionally substituted group may have a substituent at
each substitutable position of the group, and each
substitution is independent of the other.
The term "aliphatic" as used herein means
straight-chain, branched or cyclic C1-C12 hydrocarbons
which are completely saturated or which contain one or
more units of unsaturation but which are not aromatic.
For example, suitable aliphatic groups include
substituted or unsubstituted linear, branched or cyclic
alkyl, alkenyl, alkynyl groups and hybrids thereof such
as (eyeloalkyl)alkyl, (eyeloalkenyl)alkyl or

(cycloalkyl)alkenyl. The terms "alkyl", "alkoxy",
"hydroxyalkyl", "alkoxyalkyl" , and "alkoxycarbonyl", used
alone or as part of a larger moiety includes both
straight and branched chains containing one to twelve
carbon atoms. The terms "alkenyl" and "alkynyl" used
alone or as part of a larger moiety shall include both
straight and branched chains containing two to twelve
carbon atoms. The term "cycloalkyl" used alone or as
part of a larger moiety shall include cyclic C3-C12
hydrocarbons which are completely saturated or which
contain one or more units of unsaturation, but which are
not aromatic.
The terms "haloalkyl", "haloalkeriyl" and
"haloalkoxy" means alkyl, alkenyl or alkoxy, as the case
may be, substituted with one or more halogen atoms. The
term "halogen" means F, Cl, Br, or I.
The term "heteroatom" means nitrogen, oxygen,
or sulfur and includes any oxidized form of nitrogen and
sulfur, and the quaternized form of any basic nitrogen.
Also the term ^nitrogen" includes a substitutable
nitrogen of a heterocyclic ring. As an example, in a
saturated or partially unsaturated ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen, the
nitrogen may be K (as in 3,4-dihydro-2H-pyrrolyl), NH (as
in pyrrolidinyl) or NR+ (as in N-substituted
pyrrol idinyl) .
The terms "carbocycle", "carbocyclyl",
"carbocyclo", or "carbocyclic" as used herein means an
aliphatic ring system having three to fourteen members.
The terms "carbocycle", "carbocyclyl", wcarbocyclo", or
"carbocyclic" whether saturated or partially unsaturated,
also refers to rings that are optionally substituted.
The terms "carbocycle", "carbocyclyl", "carbocyclo", or

"carbocyclic" also include aliphatic rings that are fused
to one or more aromatic or nonaromatic rings, such as in
a decahydronaphthyl or tetrahydronaphthyl, where the
radical or point of attachment is on the aliphatic ring.
The term "aryl" used alone or as part of a
larger moiety as in "aralkyl", "aralkoxy", or
"aryloxyalkyl", refers to aromatic'ring groups having
five to fourteen members, such as phenyl, benzyl,
phenethyl, 1-naphthyl, 2-naphthyl, 1-anthracyl and 2-
anthracyl. The term "aryl" also refers to rings that are
optionally substituted. The term "aryl" may be used
interchangeably with the term "aryl ring". "Aryl" also
includes fused polycyclic aromatic ring systems in which
an aromatic ring is fused to one or more rings. Examples
include 1-naphthyl, 2-naphthyl, 1-anthracyl and 2-
anthracyl. Also included within the scope of the term
"aryl", as it is used herein, is a group in which an
aromatic ring is fused to one or more non-aromatic rings,
such as in an indanyl, phenanthridinyl, or
tetrahydronaphthyl, where the radical or point of
attachment is on the aromatic ring.
The term "heterocycle", "heterocyclyl", or
"heterocyclic" as used herein includes non-aromatic ring
systems having five to fpurteen members, preferably five
to ten, in which one or more ring carbons, preferably one
to four, are each replaced by a heteroatom such as N, O,
or S. Examples of heterocyclic rings include 3-1H-
benzimidazol-2-one, (1-substituted) -2-oxo-benzimidazol-3-
yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-
tetrahydropyranyl, 3 - tetrahydropyranyl, 4-
tetrahydropyranyl, [1,3]-dioxalanyl, [1,3]-dithiolanyl,
[1,3 3 -dioxanyl, 2-tetrahydrothiophenyl, 3-
tetrahydrothiophenyl, 2-morpholinyl, 3-morpholinyl, 4-

morpholinyl, 2-thiomorpholinyl, 3-thlomorpholinyl, 4-
thiomorpholinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-
pyrrolidinyl, 1-piperazinyl, 2-piperazinyl, 1-
piperidinyl, 2 -piperidinyl, 3-piperidinyl, 4-piperidinyl,
4-thiazolidinyl, diazolonyl, N-substituted diazolonyl, l-
phthalimidinyl, benzoxanyl, benzopyrrolidinyl,
benzopiperidinyl, benzoxolanyl, benzothiolanyl, and
benzothianyl. Also included within the scope of the term
"heterocyclyl" " or "heterocyclic", as it is used herein,
is a group in which a non-aromatic heteroatom-containing
ring is fused to one. or more aromatic or non-aromatic
rings, such as in an indolinyl, chromanyl,
phenanthridinyl, or tetrahydroquinolinyl, where the
radical or point of attachment is on the non-aromatic
heteroatom-containing ring. The term "heterocycle",
"heterocyclyl", or "heterocyclic" whether saturated or
partially unsaturated, also refers to rings that are
optionally substituted.
The term "heteroaryl", used alone or as part of
a larger moiety as in "beteroaralkyl" or
"heteroarylalkoxy", refers to heteroaromatic ring groups
having five to fourteen members. Examples of heteroaryl
rings include 2-furanyl, 3-furanyl, N-imidazolyl, 2-
imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-
isoxazolyl, 5-isoxazolyl, 2-oxadiazolyl, 5-oxadiazolyl,
2-oxazolyl, 4-oxazolyl, 5-oxazolyl, l-pyrrolyl, 2-
pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyfidyl, 2-
pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 3-pyridazinyl, 2-
thiazolyl, 4-thiazolyl, 5-thiazolyl, 5-tetrazolyl, 2-
triazolyl, 5-triazolyl, 2-thienyl, 3-thienyl, carbazolyl,
benzimidazolyl, benzothienyl, benzofuranyl, indolyl,
quinolinyl, benzotriazolyl, benzothiazolyl, .
benzooxazolyl, benzimidazolyl, isoquinolinyl, indolyl,

isoindolyl, acridinyl, or benzoisoxazoyl. Also included
within the scope of the term "heteroaryl", as it is used
herein, is a group in which a heteroatomic ring is fused
to one or more aromatic or nonaromatic rings where the
radical or point of attachment is on the heteroaromatic
ring. Examples include tetrahydroguinolinyl,
tetrahydroisoquinolinyl, and pyrido[3,4-d]pyrimidinyl.
The term "heteroaryl" also refers to rings that are
optionally substituted. The term "heteroaryl" may be
used interchangeably with the term "heteroaryl ring" or
the term "heteroaromatic".
An aryl (including aralkyl,. aralkoxy,
aryloxyalkyl and the like) or heteroaryl (including
heteroaralkyl and heteroarylalkoxy and the like) group
may contain one or more substituents. Examples of
suitable substituents on the unsaturated carbon atom of
an aryl, heteroaryl, aralkyl, or heteroaralkyl group
include a halogen, -R°, -0R°, -SR°/ 1,2-methylene-dioxy,
1,2-ethylenedioxy, protected OH (such as acyloxy), phenyl
(Ph), substituted Ph, -O(Ph), substituted -O(Ph),
-CH2(Ph), substituted -CH2 (Ph) , -CH2CH2(Ph), substituted
-CH2CH2(Ph), -N02, -CN, -N(R°)2, -NR°C(O)R°, -NR°C (O)N(R°) 2,
-NR°CO2R°, -NR°NR°C(O)R°, -NR°NR°C (O)N(R°) 2, -NR°NR°CO2R0,
-C(O)C(O)R°, -C(O)CH2C(O)R°, -CO2R°, -C(O)R°, -C (0)N (R°) 2,
-OC(O)N(R°)2, -S(O)2R°, -SO2N(R°)2/ -S (0) R°, -NR°SO2N (R°) 2/
-NR°S02R°, -C(=S)N(R°)2, -C (=NH)-N(R°) 2, - (CH2)yNHC (0)R°,
- (CH2)yNHC(O)CH(V-Ro) (R°) ; wherein R° is hydrogen, a
substituted or unsubstituted aliphatic group, an
unsubstituted heteroaryl or heterocyclic ring, phenyl
(Ph) , substituted Ph, -O(Ph), substituted -O(Ph),
-CH2(Ph), or substituted -CH2(Ph); y is 0-6; and V is a
linker group. Examples of substituents on the aliphatic

group or the phenyl ring of R° include amino, alkylamino,
dialkylamino, aminocarbonyl, halogen, alkyl,
alkylaminocarbonyl, dialkylaminocarbonyl,
alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkoxy,
nitro, cyano, carboxy, alkoxycarbonyl, alkylcarbonyl,
hydroxy, haloalkoxy, or haloalkyl.
An aliphatic group or a non-aromatic
heterocyclic ring may contain one or more substituents.
Examples of suitable substituents on the saturated carbon
of an aliphatic group or of a non-aromatic heterocyclic
ring include those listed above for the unsaturated
carbon of an aryl or heteroaryl group and the following:
=0, =S, =NNHR*, =NN(R*)2, =N-, =NNHC(O)R*, =NNHC02 (alkyl) ,
s=NNHSO2 (alkyl) , or =NR*, where each R* is independently
selected from hydrogen, an unsubstituted aliphatic group
or a substituted aliphatic group. Examples of
substituents on the aliphatic group include amino,
alkylamino, dialkylamino, aminocarbonyl, halogen, alkyl,
alkylaminocarbonyl, dialkylaminocarbonyl,
alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkoxy,
nitro, cyano, carboxy, alkoxycarbonyl, alkyl carbonyl,
hydroxy, haloalkoxy, or haloalkyl.
Suitable substituents on the nitrogen of a non-
aromatic heterocyclic ring include -R+, -N(R+)2/ -C(O)R+,
-CO2R+, -C(O)C(O)R+, -C(O)CH2C(O)R+, -SO2R+, -SO2N(R+)2,
-C(=S)N(R+)2, -C(=NH) -N(R+)2/ and -NR+SO2R+; wherein R+ is
hydrogen, an aliphatic group, a substituted aliphatic
group, phenyl (Ph) , substituted Ph,
-O(Ph), substituted -0 (Ph) , CH2(Ph), substituted CH2(Ph) ,
or an unsubstituted heteroaryl or heterocyclic ring.
Examples of substituents on the aliphatic group or the
phenyl ring include amino, alkylamino, dialkylamino,
aminocarbonyl, halogen, alkyl, alkylaminocarbonyl,

dialkylaminocarbonyl, alkylaminocarbonyloxy,
dialkylaminocarbonyloxy, alkoxy, nitro, cyano, carboxy,
alkoxycarbonyl, alkylcarbonyl, hydroxy, haloalkoxy, or
haloalkyl.
The term *linker group" or "linker" means an
organic moiety that connects two parts of a compound.
Linkers are typically comprised of an atom such as oxygen,
or sulfur, a unit such as -NH-, -CH2-, -C(0)-, -C(O)NH-,
or a chain of atoms, such as an alkylidene chain. The
molecular mass of a linker is typically in the range of
about 14 to 200, preferably in the range of 14 to 96 with
a length of up to about six atoms. Examples of linkers
include a saturated or unsaturated Ci-6 alkylidene chain
which is optionally substituted, and wherein one or two
saturated carbons of the chain are optionally replaced by
-0(0)-, -C(O)C(O)-, -CONH-, -CONHNH-, -C02-, -OC(O)-,
-NHCOa-, -O-, -NHCONH-, -OC(O)NH-, -NHNH-, -NHCO-, -S-,
-SO-, -S02-, -3SH-, -SO2NH-, or -NHSO2- .
The term "alkylidene chain" refers to an
optionally substituted, straight or branched carbon chain
that may be fully saturated or have one or more units of
unsaturation. The optional substituents are as described
above for an aliphatic group.
A combination of substituents or variables is
permissible only if such a combination results in a
stable or chemically feasible compound. A stable
compound or chemically feasible compound is one in which
the chemical structure is not substantially altered when
kept at a temperature of 40 °C or less, in the absence of
moisture or other chemically reactive conditions, for at
least a week.
Unless otherwise stated, structures depicted
herein are also meant to include all stereochemical forms

of the structure; i.e., the R and S configurations for
each asymmetric center. Therefore, single stereochemical
isomers as well as enantiomeric and diastereomeric
mixtures of the present compounds are within the scope of
the invention. Unless otherwise stated, structures
depicted herein are also meant to include compounds which
differ only in the presence of one or more isotopically
enriched atoms. For example, compounds having the
present structures except for the replacement of a
hydrogen by a deuterium or tritium, or the replacement of
a carbon by a 13C- or 14C-enriched carbon are within the
scope -of this invention.
Compounds of formula I or salts thereof may be
formulated into compositions. In a preferred embodiment,
the composition is a pharmaceutical composition. In one
embodiment, the composition comprises an amount of the
protein kinase inhibitor effective to inhibit a protein
kinase, particularly GSK-3, in a biological sample or in
a patient. In another embodiment, compounds of this
invention and pharmaceutical compositions thereof, which
comprise an amount of the protein kinase. inhibitor
effective to treat or prevent a GSK-3-mediated condition
and a pharmaceutically acceptable carrier, adjuvant, or
vehicle, may be formulated for administration to a
patient.
The term "GSK-3-mediated condition" or
"disease", as used herein, means any disease or other
deleterious condition or state in which GSK-3 is known to
play a role. Such diseases or conditions include.,
without limitation, diabetes, Alzheimer's disease,
Huntington's Disease, Parkinson's Disease, AIDS-
associated dementia, amyotrophic lateral sclerosis (AML),

multiple sclerosis (MS), schizophrenia, cardiomycete
hypertrophy, reperfusion/ischemia, and baldness.
One aspect of this invention relates to a
method of enhancing glycogen synthesis and/or lowering
blood levels of glucose in a patient in need thereof,
which method comprises administering to the patient a
therapeutically effective amount of a compound of formula
I or a pharmaceutical composition thereof. This method
is especially useful for diabetic patients. Another
method relates to inhibiting the production of
hyperphosphorylated Tau protein, which is useful in
halting or slowing the progression of Alzheimer's
disease. Another method relates to inhibiting the
phosphorylation of ?-catenin, which is useful for
treating schizophrenia.
Another aspect of the invention relates to
inhibiting GSK-3 activity in a biological sample, which
method comprises contacting the biological sample with a
GSK-3 inhibitor of formula I.
Another aspect of this invention relates to a
method of inhibiting Aurora-2 activity in a patient,
which method comprises administering to the patient a
compound of formula I or a composition comprising said
compound.
Another aspect of this invention relates to a
method of treating or preventing an Aurora-2-mediated
disease with an Aurora-2 inhibitor, which method
comprises administering to a patient in need of such a
treatment a therapeutically effective amount of a
compound of formula I or a pharmaceutical composition
thereof.
The term "Aurora-2-mediated condition" or
"disease", as used herein, means any disease or other

deleterious condition in which Aurora is known to play a
role. The term "Aurora-2-mediated condition" or
"disease" also means those diseases or conditions that
are alleviated by treatment with an Aurora-2 inhibitor.
Such conditions include, without limitation, cancer. The
term "cancer" includes, but is not limited to the
following cancers: colon and ovarian.
Another aspect of the invention relates to
inhibiting Aurora-2 activity in a biological sample,
which method comprises contacting the biological sample
with the Aurora-2 inhibitor of formula I, or a
composition thereof.
Another aspect of this invention relates to a
method of treating or preventing a CDK-2-mediated
diseases with a CDK-2 inhibitor, which method comprises
administering to a patient in need of such a treatment a
therapeutically effective amount of a compound of formula
I or a pharmaceutical composition thereof.
The term "CDK-2-mediated condition" or
"disease", as used herein, means any disease or other
deleterious condition in which CDK-2 is known to play a
role. The term "CDK-2-mediated condition" or "disease"
also means those diseases or conditions that are
alleviated by treatment with a CDK-2 inhibitor. Such
conditions include, without limitation, cancer,
Alzheimer's disease, restenosis, angiogenesis,
glomerulonephritis, cytomegalovirus, HIV, herpes,
psoriasis, atherosclerosis, alopecia, and autoimmune
diseases"such as rheumatoid arthritis. See Fischer, P.M.
and Lane, D.P., Current Medicinal Chemistry, 7, 1213-1245
(2000); Mani, S., Wang, c., Wu, K., Francis, R. and
Pe.stell, R., Exp. Opin. Invest. Drugs, 9, 1849 (2000);
Fry, D.W. and Garrett, M.D. , Current Opinion in

Oncologic, Endocrine & Metabolic Investiga.tiona.1 Drugs,
2, 40-59 (2000).
Another aspect of the invention relates to
inhibiting CDK-2 activity in a biological sample or a
patient, which method comprises administering to the
patient a compound of formula I or a composition
comprising said compound.
Another aspect of this invention relates to a
method of treating or preventing an ERK-2-mediated
diseases with an ERK-2 inhibitor, which method comprises
administering to a patient in need of such a treatment a
therapeutically effective amount of a compound of formula
I or a pharmaceutical composition thereof.
The term wERK-mediated condition", as used
herein means any disease state or other deleterious
condition in which ERK is known to play a role. The term
ERK-2-mediated condition" or "disease" also means those
diseases or conditions that are alleviated by treatment
with a ERK-2 inhibitor. Such conditions include, without
limitation, cancer, stroke, diabetes, hepatomegaly,
cardiovascular disease including cardiomegaly,
Alzheimer's disease, cystic fibrosis, viral disease,
autoimmune diseases, atherosclerosis, restenosis,
psoriasis, allergic disorders including asthma,
inflammation, neurological disorders and hormone-related
diseases. The term "cancer" includes, but is not limited
to the following cancers: breast, ovary, cervix,
prostate, testis, genitourinary tract, esophagus, larynx,
glioblastoma, neuroblastoma, stomach, skin,
keratoacanthoma, lung, epidermoid carcinoma, large cell
carcinoma, small cell carcinoma, lung adenocarcinoma,
bone, colon, adenoma, pancreas, adenocarcinoma, thyroid,
follicular carcinoma, undifferentiated carcinoma,

papillary carcinoma, seminoma, melanoma, sarcoma, bladder
carcinoma, liver carcinoma and biliary passages, kidney
carcinoma, myeloid disorders, lymphoid disorders,
Hodgkin's, hairy cells, buccal cavity and pharynx (oral) ,
lip, tongue, mouth, pharynx, small intestine, colon-
rectum, large intestine, rectum, brain and central
nervous system, and leukemia. ERK-2 protein kinase and
its implication in various diseases has been described
[Bokemeyer et al. 1996, Kidney Int. 49, 1187; Anderson et
al., 1990, Nature 343, 651; Crews et al., 1992, Science
258, 478; Bjorbaek et al., 1995, J. Biol. Chem. 270,
18848; Rouse et al., 1994, Cell 78, 1027; Raingeaud et
al., 1996, Mol. Cell Biol. 16, 1247; Raingeaud et al.
1996; Chen et al., 1993 Proc. Natl. Acad. Sex. USA 90,
10952; Oliver et al., 1995, Proc. Soc. Exp. Biol. Med.
210, 162; Moodie et al., 1993, Science 260, 1658; Frey
and Mulder, 1997, Cancer Res. 57, 628; Sivaraman et al.,
1997, J Clin. Invest. 99, 1478; Whelchel et al., 1997,
Am. J. Respir. Cell Mol. Biol. 16, 589].
Another aspect of the invention relates to
inhibiting ERK-2 activity in a biological sample or a
patient, which method comprises administering to the
patient a compound of formula I or a composition
comprising said compound.
Another aspect of this invention relates to a
method of treating or preventing an AKT-mediated diseases
with an AKT inhibitor, which method comprises
administering to a patient in need of such a treatment a
therapeutically effective amount of a compound of formula
I or a pharmaceutical composition thereof.
The term "AKT-mediated condition", as used
herein, means any disease state or other deleterious
condition in which AKT is known to play a role. The term

"AKT-mediated condition" or "disease" also means those
diseases or conditions that are alleviated by treatment
with a AKT inhibitor. AKT-mediated diseases or
conditions include, but are not limited to, proliferative
disorders, cancer, and neurodegenerative disorders. The
association of AKT, also known as protein kinase B, with
various diseases has been described [Khwaja) A., .Nature,
pp. 33-34, 1990; Zang, Q. Y., et al, Oncogene, 19 2000;
Kazuhiko, N., et al, The Journal of Neuroscience, 20
2000] .
Another aspect of the invention relates to
inhibiting AKT activity in a biological sample or. a
patient, which method comprises administering to the
patient a compound of formula I or a composition
comprising said compound.
Another aspect of this invention relates to a
method of treating or preventing a Src-mediated disease
with a Src inhibitor, which method comprises
administering to a patient in need of such a treatment a
therapeutically effective amount of a compound of formula
I or a pharmaceutical composition thereof.
The term wSrc-mediated condition", as used
herein means any disease state or other deleterious
condition in which Src is known to play a role. The term
"Src-mediated condition" or "disease" also means those
diseases or conditions that are alleviated by treatment
with a Src inhibitor. Such conditions include, without
limitation, hypercalcemia, osteoporosis, osteoarthritis,
cancer, symptomatic treatment of bone metastasis, and
Paget's disease. Src protein kinase and its implication
in various diseases has been described [Soriano, Cell,
69, 551 (1992); Soriano et al., Cell, 64, 693 (1991);
Takayanagi, J. Clin. Invest., 104, 137 (1999); Boschelli,

Drugs of the Future 2000, 25(7), 717, (2000); Talamonti,
J. Clin. Invest., 91, 53 (1993); Lutz, Biochem. Biophys.
Res. 243, 503 (1998); Rosen, J. Biol. Chem., 261, 13754
(1986); Bolen, Proc. Natl. Acad. Sci. USA, 84, 2251
(1987); Masaki, Hepatology, 27, 1257 (1998); Biscardi,
Adv. Cancer Res., 76, 61 (1999); Lynch, Leukemia, 7, 1416
(1993); Wiener, Clin. Cancer Res., 5, 2164 (1999);
Staley, Cell Growth Diff., 8, 269 (1997)].
Another aspect of the invention relates to
inhibiting Src activity in a biological sample or a
patient, which method comprises administering to the
patient a compound of formula I or a composition
comprising said compound.
The term "pharmaceutically acceptable carrier,
adjuvant, or vehicle" refers to a non-toxic carrier,
adjuvant, or vehicle that may be administered to a
patient, together with a compound of this invention, and
which does not destroy the pharmacological activity
thereof.
The term "patient" includes human and
veterinary subjects.
The term "biological sample", as used herein,
includes, without limitation, cell cultures or extracts
thereof; preparations of an enzyme suitable for in vitro
assay; biopsied material obtained from a mammal or
extracts thereof;" and blood, saliva, urine, feces, semen,
tears, or other body fluids or extracts thereof.
The amount effective to inhibit protein kinase
for example, GSK-3 and Aurora-2, is one that measurably
inhibits the kinase activity where compared to the
activity of the enzyme in the absence of an inhibitor.-
Any method may be used to determine inhibition, such as,

for example, the Biological Testing Examples described
below.
Pharmaceutically acceptable carriers that may
be used in these pharmaceutical compositions include, but
are not limited to, ion exchangers, alumina, aluminum
stearate, lecithin, serum proteins, such as human serum
albumin, buffer substances such as phosphates, glycine,
sorbic acid," potassium sorbate, partial glyceride
mixtures of saturated vegetable fatty acids, water, salts
or electrolytes, such as protamine sulfate, disodium
hydrogen phosphate, potassium hydrogen phosphate, sodium
chloride, zinc salts, colloidal silica, magnesium
trisilicate, polyvinyl pyrrolidone, cellulose-based
substances, polyethylene glycol, sodium
carboxymethylcellulose, polyacrylates, waxes,
polyethylene-polyoxypropylene-block polymers,
polyethylene glycol and wool fat.
The compositions of the present invention may
be administered orally, parenterally, by inhalation
spray, topically, rectally, nasally, buccally, vaginally
or via an implanted reservoir. The term "parenteral" as
used herein includes subcutaneous, intravenous,
int r amus cular, intra - articular, intra - synovial,
intrasternal, intrathecal, intrahepatic, intralesional
and intracranial injection or infusion techniques.
Preferably, the compositions are administered orally,
intraperitoneally or intravenously.
Sterile injectable forms of the compositions of
this invention may be aqueous or oleaginous suspension.
These suspensions may be formulated according to
techniques known in the art using suitable dispersing or
wetting agents and suspending agents. The sterile
injectable preparation may also be a sterile injectable

solution or suspension in a non-toxic parenterally-
acceptable diluent or solvent, for example as a solution
in 1,3-butanediol. Among the acceptable vehicles and
solvents that may be employed are water, Ringer's
solution and isotonic sodium chloride solution. In
addition, sterile, fixed oils are conventionally employed
as a solvent or suspending medium. For this purpose, any
bland fixed oil may be employed including synthetic mono-
or di-glycerides. Fatty acids, such as oleic acid and
its glyceride derivatives are useful in the preparation
of injectables, as are natural pharmaceutically-
acceptable oils, such as olive oil or castor oil,
especially in their polyoxyethylated versions. These oil
solutions or suspensions may also contain a long-chain
alcohol diluent or dispersant, such as carboxymethyl
cellulose or similar dispersing agents which are commonly
used in the formulation of pharmaceutically acceptable
dosage forms including emulsions and suspensions. Other
commonly used surfactants, such as Tweens, Spans and
other emulsifying agents or bioavailability enhancers
which are commonly used in the manufacture of
pharmaceutically acceptable solid, liquid, or other
dosage forms may also be used for the purposes of
formulation.
The pharmaceutical compositions of this
invention may be orally administered in any orally
acceptable dosage form including, but not limited to,
capsules, tablets, aqueous suspensions or solutions. In ?
the case of tablets for oral use, carriers commonly used
include lactose and corn starch. Lubricating agents,
such as magnesium stearate, are also typically added.
For oral administration in a capsule form, useful
diluents include lactose and dried cornstarch. When

aqueous suspensions are required for oral use, the active
ingredient is combined with emulsifying and suspending
agents. If desired, certain sweetening, flavoring or
coloring agents may also be added.
Alternatively, the pharmaceutical compositions
of this invention may be administered in the form of
suppositories for rectal administration. These can be
prepared by mixing the agent with a suitable non-
irritating excipient which is solid at room temperature
but liquid at rectal temperature and therefore will melt
in the rectum to release the drug. Such materials
include cocoa butter, beeswax and polyethylene glycols.
The pharmaceutical compositions of this
invention may also be administered topically, especially
when the target of treatment includes areas or organs
readily accessible by topical application, including
diseases of the eye, the skin, or the lower intestinal
tract. Suitable topical formulations are readily
prepared for each of these areas or organs.
Topical application for the lower intestinal
tract can be effected in a rectal suppository formulation
(see above) or in a suitable enema formulation.
Topically-transdermal patches may also be used.
For topical applications, the pharmaceutical
compositions may be formulated in a suitable ointment
containing the active component suspended or dissolved in
one or more carriers. Carriers for topical
administration of the compounds of this invention
include, but are not limited to, mineral oil, liquid
petrolatum, white petrolatum, propylene glycol,
polyoxyethylene, polyoxypropylene compound, emulsifying
wax and water. Alternatively, the pharmaceutical
compositions can be formulated in a suitable lotion or

cream containing the active components suspended or
dissolved in one or more pharmaceutically acceptable
carriers. Suitable carriers include, but are not limited
to, mineral oil, sorbitan monostearate, polysorbate 60,
cetyl esters wax, cetearyl alcohol, 2-octyldodecanol,
benzyl alcohol and water.
For ophthalmic use, the pharmaceutical
compositions may be formulated as micronized suspensions
in isotonic, pH adjusted sterile saline, or, preferably,
as solutions in isotonic, pH adjusted sterile saline,
either with or without a preservative such as
benzylalkonium chloride. Alternatively, for ophthalmic
uses, the pharmaceutical compositions may be formulated
in an ointment such as petrolatum.
The pharmaceutical compositions of this
invention may also be administered by nasal aerosol or
inhalation. Such compositions are prepared according to
techniques well-known in the art of pharmaceutical
formulation and may be prepared as solutions in saline,
employing benzyl alcohol or other suitable preservatives,
absorption promoters to enhance bioavailability,
fluorocarbons, and/or other conventional solubilizing or
dispersing agents.
In addition to the compounds of this invention,
pharmaceutically acceptable derivatives or prodrugs of
the compounds of this invention may also be employed in
compositions to treat or prevent the above-identified
diseases or disorders.
A "pharmaceutically acceptable derivative or
prodrug" means any pharmaceutically acceptable salt,
ester/ salt of an ester or other derivative of a compound
of this invention which, upon administration to a
recipient, is capable of providing, either directly or

indirectly, a compound of this invention or an
inhibitorily active metabolite or residue thereof.
Particularly favored derivatives or prodrugs are those
that increase the bioavailability of the compounds of
this invention when such compounds are administered to a
patient (e.g., by allowing an orally administered
compound to be more readily absorbed into the blood) or
which enhance delivery of the parent compound to a
biological compartment (e.g., the brain or lymphatic
system) relative to the parent species.
Pharmaceutically acceptable prodrugs of the
compounds of this invention include, without limitation,
esters, amino acid esters, phosphate esters, metal salts
and sulfonate esters.
Pharmaceutically acceptable salts of the
compounds of this invention include those derived from
phaxmaceutically acceptable inorganic and organic acids
and bases. Examples of suitable acid salts include
acetate, adipate, alginate, aspartate, benzoate,
benzenesulfonate, bisulfate, butyrate, citrate,
camphorate, camphorsulfonate, cyclopentanepropionate,
digluconate, dodecylsulfate, ethanesulfonate, formate,
fumarate, glucoheptanoate, glycerophosphate, glycolate,
hemisulfate, heptanoate, hexanoate, hydrochloride,
hydrobromide, hydroiodide, 2-hydroxyethanesulfonate,
lactate, maleate, malonate, methanesulfonate, 2-
naphthalenesulfonate, nicotinate, nitrate, oxalate,
palmoate, pectinate, persulfate, 3-phenylpropionate,
phosphate, picrate, pivalate, propionate, salicylate,
succinate, sulfate, tartrate, thiocyanate, tosylate and
undecanoate. Other acids, such as oxalic, while not in
themselves pharmaceutically acceptable, may be employed
in the preparation of salts useful as intermediates in

obtaining the compounds of the invention and their
pharmaceutically acceptable acid addition salts.
Salts derived from appropriate bases include
alkali metal (e.g., sodium and potassium), alkaline earth
metal (e.g., magnesium), ammonium and N+(C1_4 alkyl)4
salts. This invention also envisions the quaternization
of any basic nitrogen-containing groups of the compounds
disclosed herein. Water or oil-soluble or dispersible
products may be obtained by such quaternization.
The amount of the protein kinase inhibitor that
may be combined with the carrier materials to produce a
single dosage form will vary depending upon the patient
treated and the particular mode of administration.
Preferably, the compositions should be formulated so that
a dosage of between 0.01 - 100 mg/kg body weight/day of
the inhibitor can be administered to a patient receiving
these compositions.
It should also be understood that a specific
dosage and treatment regimen for any particular patient
will depend upon a variety of factors, including the
activity of the specific compound employed, the age, body
weight, general health, sex, diet, time of
administration, rate of excretion, drug combination, and
the judgment of the treating physician and the severity
of the particular disease being treated. The amount of
the inhibitor will also depend upon the particular
compound in the composition.
Depending upon the particular protein kinase-
mediated condition to be treated or prevented, additional
therapeutic agents, which are normally administered to
treat or prevent that condition, may be administered
together with the inhibitors of this invention. For
example, in the treatment of diabetes other anti-diabetic

agents may be combined with the GSK-3 inhibitors of this
invention to treat diabetes. These agents include,
•without limitation, insulin or insulin analogues, in
injectable or inhalation form, glitazones, alpha
glucosidase inhibitors, biguanides, insulin sensitizers,
and sulfonyl ureas.
Other examples of agents the inhibitors of this
invention may also be combined with include, without
limitation, chemotherapeutic agents or other anti-
proliferative agents such as adriamycin, dexamethasone,
vincristine, cyclophosphamide, fluorouracil, topotecan,
taxol, interferons, and platinum derivatives; anti-
inflammatory agents such as corticosteroids, TNF
blockers, IL-1 KA, azathioprine, cyclophosphamide, and
sulfasalazine; immunomodulatory and immunosuppressive
agents such as cyclosporin, tacrolimus, rapamycin,
mycophenolate mofetil, interferons, corticosteroids,
cyclophophamide, azathioprine, and sulfasalazine;
neurotrophic factors such as acetylcholinesterase
inhibitors, MAO inhibitors, interferons, anti-
convulsants, ion channel blockers, riluzole, and anti-.
Parkinsonian agents; agents for treating cardiovascular
disease such as beta-blockers, ACE inhibitors, diuretics,
nitrates, calcium channel blockers, and statins; agents
for treating liver disease such as corticosteroids,
cholestyramine, interferons, and anti-viral agents;
agents for treating blood disorders such as
corticosteroids, anti-leukemic agents, and growth
factors; and agents for treating immunodeficiency
disorders such as gamma globulin.
Those additional agents may be administered
separately from the protein kinase inhibitor-containing
composition, as part of a multiple dosage regimen.

Alternatively, those agents may be part of a single
dosage form, mixed together with the protein kinase
inhibitor of this invention in a single composition.
Compounds of this invention may exist in
alternative tautomeric forms, as in tautomers 1 and 2
shown below. Unless otherwise indicated, the
representation of either tautomer is meant to include the
other.

Rx and Ry (at positions Z3 and Z4, respectively)
may be taken together to form a fused ring, providing a
bicyclic ring system containing Ring A. Preferred Rx/Ry
rings include a 5-, 6-, 7-, or 8-membered unsaturated or
partially unsaturated ring having 0-2 heteroatoms,
wherein said Rx/Ry ring is optionally substituted.
Examples of Ring A systems are shown below by compounds
I-A through I-DD, wherein Z1 is nitrogen or C(R9) and Z2
is nitrogen or C(H).

Preferred bicyclic Ring A systems include I-A,
I-B, I-C, I-D, I-E, I-F, I-G, I-H, I-I, I-J, I-K, I-L,
and I-M, more preferably I-A, I-B, i-c, I-F, and I-H, and
most preferably I-A, I-B, and I-H.
In the monocyclic Ring A system, preferred Rx
groups, when present, include hydrogen, alkyl- or
dialkylamino, acetamido, or a C1_4 aliphatic group such as
methyl, ethyl, cyclopropyl, isopropyl or t-butyl.
Preferred Ry groups, when present, include T-R3 wherein T
is a valence bond or a methylene, and R3 is -R, -N(R4)2,

or -OR. Examples of preferred Ry include 2-pyridyl, 4-
pyridyl, piperidinyl, methyl, ethyl, cyclopropyl,
isopropyl, t-butyl, alkyl- or dialkylamino, acetamido,
optionally substituted phenyl such as phenyl or halo-
substituted phenyl, and methoxymethyl.
In the bicyclic Ring A system, the ring formed
when RX and Ry are taken together may be substituted or
unsubstituted. Suitable substituents include -R, halo,
-OR, -C(=O)R, -CO2R, -COCOR, -N02/ -CN, -S(O)R, -S02R,
-SR, -N(R4)2/ -CON(R4)2, -SO2N(R4)2, -O.C(=O)R, -N(R4)COR,
-N(R4) C02(optionally substituted C1-6 aliphatic) ,
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2,
-N(R4)SO2N(R4)2/ -N(R4)SO2R, or -OC (=O)N(R4) 2, wherein R and
R4 are as defined above. Preferred Rx/Ry ring
substituents include -halo, -R, -OR, -COR, -CO2R,
-CON(R4)2/ -CN, or -N(R4)2 wherein R is hydrogen or an
optionally substituted C1-g aliphatic group.
R2 and R2' may be taken together to form a fused
ring, thus providing a bicyclic ring system containing a
pyrazole ring. Preferred fused rings include benzo,
pyrido, pyrimido, and a partially unsaturated 6-membered
carbocyclo ring, wherein said fused ring is optionally
substituted. These are exemplified in the following
formula I compounds having a pyrazole-containing bicyclic
ring system:

Preferred substituents on the R2/R2' fused ring
include one or more of the following: -halo, -N(R4)2/ -C1_3
alkyl, -Ca-3 haloalkyl, -NO2, -0(C1-3 alkyl) , -CO2(C1-3
alkyl) , -CN, -SO2 (C1-3 alkyl) , -SO2NH2, -OC(O)NH2/ -
NH2SO2(C1_3 alkyl) , -NHC(O) (C1-3 alkyl) , -C(O)NH2, and-CO(Ci-
3 alkyl) , wherein the (C1-3 alkyl) is most preferably
methyl.
When the pyrazole ring system is monocyclic,
preferred R2 groups include hydrogen, C1-4 aliphatic,
alkoxycarbonyl, (un) substituted phenyl, hydroxyalkyl,
alkoxyalkyl, aminocarbonyl, mono- or
dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl,
dialkylaminoalkyl, phenylaminocarbonyl, and (N-
heterocyclyl) carbonyl. Examples of such preferred R2
substituents include methyl, cyclopropyl, ethyl,
isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H,
CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3,
CH2CH2CH20CH2Ph, CH2CH2CH2NH2/ CH2CH2CH2NHCOOC (CH3)3/
CONHCH(CH3.)2/ CONHCH2CH=CH2, CONHCH2CH2OCai3, CONHCH2Ph,
CONH (cyclohexyl) , CON (Et) 2, CON (CH3) CH2Ph, CONH (n- C3H7) ,
CON(Et)CH2CH2CH3, CONHCH2CH (CH3) 2, CON (n-C3H7) 2, CO(3-
methoxymethylpyrrolidin-1-yl) , CONH(3-tolyl) , CONH(4-
tolyl) , CONHCH3, CO(morpholin-l-yl) , C0(4-methylpiperazin-
1-yl) , CONHCH2CH2OH, CONH2, and CO (piperidin-1-yl) . A
preferred R2' group is hydrogen.
An embodiment that is particularly useful for
treating GSK3 -mediated diseases relates to compounds of
formula II:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any subs ti tut able non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8;
R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R8, said C1-6 aliphatic group optionally,
substituted with halo, cyano, nitro, or oxygen, or R1
and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with the.ir intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8

membered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
substituted by oxo or T-R3, and any substitutable
nitrogen on said ring formed by Rx and Ry is
substituted by R4;
T is a valence bond or a C1_4 alkylidene chain;
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -N02, -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -NO2, -CN, -S(O)R, -S(0)2R, -SR,
-N(R4)2, -CON(R7)2, -SO2N(R7)2,-OC(=O)R, -N(R7)COR,
-N(R7)C02 (optionally substituted QL-G aliphatic),
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R7) CON (R7) 2,
-N(R7)SO2N(R7)2, -N(R4)SO2R7 or -OC (=O)N(R7) 2;
each R is independently selected from hydrogen or an
optionally substituted group selected from Ci-6
aliphatic, C6.10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected, from -R7, -COR7,
-CO2 (optionally substituted d-e aliphatic) , -CON(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;

each R5 is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -N02/ -CN, -S(O)R, -SO2R, -SR,
-N(R4)2, -C0N(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR,
-N(R4)CO2 (optionally substituted Ci-6 aliphatic),
-N(R4)N(R4)2, -C=NN(R4)2/ -C=N-OR, -N(R4) CON(R4)2,
-N(R4)SO2N(R4)2, -N{R4)SO2R, or -OC (=O)N(R4) 2/ or R5 and
an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
V is -O-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(Re)-,
-N(R6)-, -CO-, -CQ2-, -N(R6)CO-, -N(R6)C(O)O-,
-N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(R6)N(R6) -,
-C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(R6)2S-,
-C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6)2N(R6)-,
-C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN(R6) - ,
-C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C(R6) 2N(R6) SO2N(R6) - , or
-C (R6) 2N (R6) CON (R6) - ;
W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-,
-C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-,
-C(R6)OC(O)-, -C(R6)OC(O)N(R6)-, -C(R6) 2N(R6) CO-,
-C(R6)2N(R6)C(O)O-, -C(Re)=NN(R6)-, -C(R6)=N-O-,
-C(R6)2N(R6)N(R6)-, -C(R6)2N(R6)SO2N(R6)-,
-C(R€)2N(R€)CON(R6)-, or -CON(R6)-;
each R€ is independently selected from hydrogen, an
optionally substituted Ca_4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen.to form a 5-8 membered heterocyclyl or
heteroaryl ring; and

each R8 is independently selected from an optionally
substituted C1_4 aliphatic group, -OR6, -SR6, -COR6,
-SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or
-CO2R6.
When the Rx and RY groups of formula II are
taken together to form a fused ring, preferred R*/Ry rings
include a 5-, 6-, 7-, or 8-membered unsaturated or
partially unsaturated ring having 0-2 heteroatoms,
wherein said R*/Ry ring is optionally substituted. This
provides a bicyclic- ring system containing a pyrimidine
ring. Examples of preferred pyrimidine ring systems of
formula II are the mono- and bicyclic systems shown
below.

More preferred pyrimidine ring systems of
formula II include II-A, II-B, II-C, II-F, and II-H, most
preferably II-A, II-B, andll-H.
In the monocyclic pyrimidine ring system of
formula II, preferred R* groups include hydrogen, alkyl-
or dialkylamino, acetamido, or a Ci_4 aliphatic group such
as methyl, ethyl, cyclopropyl, isopropyl or t-butyl.
Preferred Ry groups include T-R3 wherein T is a valence
bond or a methylene, and R3 is -R, -N(R4)2/ or -OR. When
R3 is -R or -OR, a preferred R is an optionally
substituted group selected from C1-6 aliphatic, phenyl, or
a 5-6 membered heteroaryl or heterocyclyl ring. Examples
of preferred Ry include. 2-pyridyl, 4-pyridyl, piperidinyl,
methyl, ethyl, cyclopropyl, isopropyl, t-butyl, alkyl- or
dialkylamino, acetamido, optionally substituted phenyl

such as phenyl or halo-substituted phenyl, and
methoxymethyl.
In the bicyclic pyrimidine ring system of
formula II, the ring formed when Rx and Ry are taken
together may be substituted or unsubstituted. Suitable
substituents include -R, halo, -OR, -C(=O)R, -CO2R,
-COCOR, -N02/ -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2,
-SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N (R4) C02 (optionally
substituted C1-c aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2,
-C=N-OR, -N(R4)CON(R4)2, -N(R4) SO2N(R4) 2/ -N(R4) SO2R, or
-OC(=O)N(R4)2, wherein R and R4 are as defined above.
Preferred Rx/Ry ring substituents include -halo, -R, -OR,
-COR, -CO2R, -CON(R4)2, -CN, or -N(R4)2 wherein R is an
optionally substituted d-g aliphatic group.
The R2 and R2' groups of formula II may be taken
together to form a fused ring, thus providing a bicyclic
ring system containing a pyrazole ring. Preferred fused
rings include benzo, pyrido, pyrimido, and a partially
unsaturated 6-membered carbocyclo ring. These are
exemplified in the following formula II compounds having
a pyrazole-containing bicyclic ring system:

Preferred substituents on the R2/R2' fused ring
of formula II include one or more of the following:
-halo, -N(R4)2, -d-4 alkyl, -cx_4 haloalkyl, -N02l -0(Cx_4
alkyl), -C02 (d-4 alkyl) , -CN, -SO2 (d_4 alkyl), -SO2NH2/

-OC(O)NH2, -NH2SO2 (C1-4 alkyl) , -NHC(O) (C1-4 alkyl) ,
-C(O)NH2/ and -CO(Ca-4 alkyl) , wherein the (Ci_4 alkyl) is a
straight, branched, or cyclic alkyl group. Preferably,
the (C1-4 alkyl) group is methyl.
When the pyrazole ring system of formula II is
monocyclic, preferred R2 groups include hydrogen, a
substituted or unsubstituted group selected from aryl,
heteroaryl, or a C1_6 aliphatic group. Examples of such
preferred R2 groups include methyl, t-butyl, -CH2OCH3,
cyclopropyl, furanyl, thienyl, and phenyl. A preferred
R2' group is hydrogen.
More preferred ring systems of formula II are
the following, which may be substituted as described
above, wherein R2 and R2' are taken together with the
pyrazole ring to form an indazole ring; and Rx and Ry are
each methyl, or Rx and Ry are taken together with the
pyrimidine ring to form a quinazoline or
tetrahydroquinazoline ring:

Particularly preferred are those compounds of formula
II-Aa, II-Ba, or II-Ha wherein ring C is a phenyl ring
and R1 is halo, methyl, or trifluoromethyl.
Preferred formula II Ring C groups are phenyl
and pyridinyl. When two adjacent substituents on Ring C
are taken together to form a fused ring, Ring C is

contained in a bicyclic ring system. Preferred fused
rings include a benzo or pyrido ring. Such rings
preferably are fused at ortho and meta positions of Ring
C. Examples of preferred bicyclic Ring C systems include
naphthyl, guinolinyl and isoguinolinyl.
An important feature of the formula II
compounds is the R1 ortho substituent on Ring C. An ortho
position on Ring C or Ring b is defined relative to the •
position where Ring A is attached. Preferred R1 groups
include -halo, an optionally substituted C1-6 aliphatic
group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(RS)2,
-CO2R6, -CONH2, -NHCOR6, -OC(0)NH2, or -NHSO2R6. When R1 is
an optionally substituted Ci-6 aliphatic group, the most
preferred optional substituents are halogen. Examples of
preferred R1 groups include -CF3, -Cl, -F, -CN, -COCH3,
-OCH3, -OH, -CH2CH3, -OCH2CH3, -CH3, -CF2CH3, cyclohexyl, t-
butyl, isopropyl, cyclopropyl, -C=CH, -C=C-CH3, -SO2CH3,
-SO2NH2, -N(CH3)2, -CO2CH3, -CONH2, -NHCOCH3, -OC(O)NH2,
-NHSO2CH3, and -OCF3.
On Ring C of formula II, preferred R5
substituents, when present, include -halo, -CN, -N02,
-N(R4)2, optionally substituted C1_6 aliphatic group, -OR,
-C(O)R, -C02R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, and
-N(R4)SO2R. More preferred R5 .substituents include -Cl,
-F, -CN, -CF3, -NH2, -NH(d-4 aliphatic), -N(C1_4
aliphatic)2, -O(C1_4 aliphatic), C1 aliphatic, and
-CO2(C1-4 aliphatic). Examples of such preferred Rs
substituents include -Cl, -F, -CN, -CF3, -NH2, -NHMe,
-NMe2, -OEt, methyl, ethyl, cyclopropyl, isopropyl, .t-
butyl, and -CO2Et.
Preferred formula II compounds have one or
more, and more preferably all, of the features selected
from the group consisting of:

(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from a
naphthyl, quinolinyl or isoquinolinyl ring;
(b) Rx is hydrogen or C1-4 aliphatic and Ry is
T-R3, or Rx and Ry are taken together with their
intervening atoms to form an optionally substituted 5-7
membered unsaturated or partially unsaturated ring having
0-2 ring nitrogens;
(c) R1 is -halo, an optionally substituted Ca_6
aliphatic group, phenyl, -COR6, -ORS, -CN, -SO2R6, -SO2NH2,
-N(R6)2/ -CO2R6, -CONH2, -NHCOR6, -QC(O)NH2, or -NHSO2RG;
and
(d) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl,
heteroaryl, or a Cx-6 aliphatic group, or R2 and R2' are
taken together with their intervening atoms to form a
substituted or unsubstituted benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring.
More preferred compounds of formula II have one
or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring;
(b) Rx is hydrogen or methyl and Ry is -R,
N(R4)2, or -OR, or Rx and Ry are taken together with their
intervening atoms to form a 5-7 membered unsaturated or
partially unsaturated carbocyclo ring optionally
substituted with -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, .
-NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2,

-SO2N(R4)2/ -OC(=O)R, -N(R4)C0R, -N(R4) CO2 (optionally
substituted d_6 aliphatic), -N(R4)N(R4)2/ -C=NN(R4)2,
-C=N-OR, -N(R4)CON(R4)2, -N(R4) SO2N(R4) 2, -N(R4)SO2R, or
-OC(=O)N(R4)2;
(c) R1 is -halo, a Ci_6 haloaliphatic group, a
Ci_6 aliphatic group, phenyl, or -CN;
(d) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl, or
a C1_6 aliphatic group, or R2 and R2' are taken together
with their intervening atoms to form a substituted or
unsubstituted benzo, pyrido, pyrimido or partially
unsaturated 6-membered carbocyclo ring; and
(e) each R5 is independently selected from
-halo, -CN, -N02/ -N(R4)2, optionally substituted C1_6
aliphatic group, -OR, -C(O)R, -CO2R, -C0NH(R4) , -N(R4)COR,
-SO2N(R4)2, or -N(R4)SO2R.
Even more preferred compounds of formula II
have one or more, and more preferably all, of the
features selected from the group consisting of:
(a) Ring C is a phenyl ring optionally
substituted by -R5;
(b) RX is hydrogen or methyl and Ry is methyl,
methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl,
alkyl- or an optionally substituted group selected from
2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry
are taken together with their intervening atoms to form
an optionally substituted benzo ring or partially
unsaturated 6-membered carbocyclo ring;
(c) R1 is -halo, a C1 aliphatic group
optionally substituted with halogen, or -CN;
(d) R2 and R2' are taken together with their
intervening atoms to form a benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring
(a)
optionally substituted with -halo, -N(R4)2, -C1-4 alkyl,
-C1-4 haloalkyl, -N02, -0(C1-4 alkyl) , -CO2(c1 alkyl) , -CN,
- SO2 (C1-4 alkyl) , - SO2NH2, -OC (O) NH2, -NH2SO2 (C1-4 alkyl) ,
-NHC(O) (C1-4 alkyl), -C(0)NH2, or -CO(CX.4 alkyl) , wherein
the (C1_4 alkyl) is a straight, branched, or cyclic alkyl
group; and
(e) each R5 is independently selected from -Cl,
-F, -C3ST, -CF3, -NH2, -NH(C1-4 aliphatic) , -N(C1-4
aliphatic)2, -O(C1-4 aliphatic), C1-4 aliphatic, and
-CO2(C1_4 aliphatic).
Representative compounds of formula II are
shown below in Table 1.

In another embodiment, this invention provides
a composition comprising a compound of formula II and a
pharmaceutically acceptable carrier.

One aspect of this invention relates to a
method of inhibiting GSK-3 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula II.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a GSK-3
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula II.
Another aspect relates to a method of enhancing
glycogen synthesis and/or lowering blood levels of
glucose in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
II. This method is especially useful for diabetic
patients.
Another aspect relates to a method of .
inhibiting the production of hyperphosphorylated Tau
protein in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
II. This method is especially useful in halting or
slowing the progression of Alzheimer's disease.
Another aspect relates to a method of
inhibiting the phosphorylation of p-catenin in a patient
in need thereof, comprising administering to said patient
a therapeutically effective amount of a composition
comprising a compound of formula II. This method is
especially useful for treating schizophrenia.
One aspect of this invention relates to a
method of inhibiting Aurora activity in a patient,

comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula II.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with an Aurora
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula II. This method is
especially useful for treating cancer, such as colon,
ovarian, and breast cancer.
One aspect of this invention relates to a
method of inhibiting CDK-2 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula II. ...
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a CDK-2
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula II. This method is
especially useful for treating cancer, Alzheimer's
disease, restenosis, angiogenesis, glomerulonephritis,
cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis,
alopecia, and autoimmune diseases such as rheumatoid
arthritis.
Another method relates to inhibiting GSK-3,
Aurora, or CDK-2 activity in a biological sample, which
method comprises contacting the biological sample with
the GSK-3 or Aurora inhibitor of formula II, or a
pharmaceutical composition thereof, in an amount
effective to inhibit GSK-3, Aurora or CDK-2.

Each of the aforementioned methods directed to
the inhibition of GSK-3, Aurora or CDK-2, or the
treatment of a disease alleviated thereby, is preferably
carried out with a preferred compound of formula II, as
described above.
Another embodiment of this invention relates to
compounds of formula III:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or
heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;
Rx and Ry are taken together with their intervening atoms
to form a fused, benzo ring or a 5-8 membered
carbocyclo ring, wherein any substitutable carbon on
said fused ring formed by Rx and Ry is substituted by
oxo or T-R3;
T is a valence bond or a C1_4 alkylidene chain;

R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2/ is substituted by R4;
R3 is selected from -R, -halo, =0, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -N02, -CN, -S(O)R, -S(0)2R, -SR,
-N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR,
-N(R4)CO2 (optionally substituted C1-6 aliphatic),
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON (R4) 2,
-N(R4)SO2N(R4)2, -N(R4)SO2R, or -0C (=0)N(R4) 2;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-C02 (optionally substituted C1-g aliphatic) , -C0N(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form, a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR,
-N(R4)2/ -CON{R4)2/ -SO2N(R4)2/ -OC(=O)R, -N(R4)COR,
-N(R4)CO2 (optionally substituted d-e aliphatic),
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R4) CON (R4) 2,
-N(R4)SO2N(R4)2, -N(R4)SO2R, or -0C (=0)N (R4) 2 ;
V.is -0-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(Re)-,
-N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N(R6) C (O) O-,

-N(R6)CON(R6)-, -N(RG)SO2N(R6)-, -N(R6)N(R6) -,
-C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(R6)2S-,
-C(Re)2SO-, -C(R6)2SO2-# -C(R6)2SO2N(R6)-, -C(R6)2N(R6) -,
-C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C(R6) =NN(R6) -,
-C(R6)=N-O-, -C{R6)2N(R6)N(R6)-, -C (R6) 2N(R6) SO2N(R6) -, or
-C(R6)2N(R6)CON(R6)-;
W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-,
-C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -C02-,
-C(R6)OC(O)-, -C(R6)OC(O)N(R6)-, -C (R6) 2N(R6) CO-,
-C(R6)2N -C (R6) 2N (R6) N (R6) - , -C (R6) 2N (R6) SO2N (R6) -,
-C(R6)2N{R6)CON(R6)-, or -CON(R6)-;
each R6 is independently selected from hydrogen or an
optionally substituted C1_4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring; and
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring.
Preferred formula III Ring D monocyclic rings
include substituted and unsubstituted phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, thienyl,
azepanyl, and morpholinyl rings. When two adjacent
substituents on Ring D are taken together to form a fused
ring, the Ring D system is bicyclic. Preferred formula
III Ring D bicyclic rings include 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl,
2,3 -dihydro- 1H-isoindolyl, 2,3 -dihydro- 1H-indolyl,
isoguinolinyl, quinolinyl, and naphthyl. Examples of

more preferred bicyclic Ring D systems include naphthyl
and isoquinolinyl.
Preferred R5 substituents on Ring D of formula
III include halo, oxo, CN, -N02, -N(R4)2, -CO2R, -CONH(R4) ,
-N(R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or
substituted or unsubstituted group selected from 5-6
membered heterocyclyl, C6-10 aryl, or C1_6 aliphatic. More
preferred R5 substituents include -halo, -CN, -oxo, -SR,
-OR, -N(R4)2/ -C(O)R, or a substituted or unsubstituted
group selected from 5-6 membered heterocyclyl, C6-10 aryl,
or C1-6 aliphatic. Examples of Ring D substituents
include -OH, phenyl, methyl, CH2OH, CH2CH2OH,
pyrrolidinyl, OPh, CF3, C=CH, Cl, Br, F, I, NH2, C(O)CH3,
i-propyl, tex-t-butyl, SEt, OMe, N(Me)2, methylene dioxy,
and ethylene dioxy.
Preferred rings formed when the Rx and Ry groups
of formula III are taken together to form a fused ring
include a 5-, 6-, or 7-membered unsaturated or partially
unsaturated carbocyclo ring, wherein any substitutable
carbon on said fused ring is substituted by oxo or T-R3.
Examples of preferred bicyclic ring systems are shown
below.

Preferred substituents on the Rx/Ry fused ring
of formula III include -R, oxo, halo, -OR, -C(=O)R, -CO2R,
-COCOR, -N02/ -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2,
-SO2N(R4)2, -OC(=O)R, -N(R4)C0R,' -N(R4) CO2 (optionally
substituted C1-6 aliphatic) , -N(R4)N(R4)2/ -C=NN(R4)2,
-C=N-OR, -N(R4)CON(R4)2, -N (R4) SO2N(R4) 2, -N(R4)SO2R, or
-OC(=O)N(R4)2|. wherein R and R4 are as defined above.
More preferred substituents on the Rx/Ry fused ring
include halo, CN, oxo, Ca-g alkyl, C1 alkoxy, (C1_6
alkyl) carbonyl, (C1.6 alkyl) sulfonyl, mono- or
dialkylamino, mono- or dialkylaminocarbonyl, mono- or
dialkylaminocarbonyloxy, or 5-6 membered heteroaryl.
Examples of such preferred substituents include methoxy,
methyl, isopropyl, methylsulfonyl, cyano, chloro,
pyrrolyl, methoxy, ethoxy, ethylamino, acetyl, and
acetamido.
Preferred R2 substituents of formula III include
hydrogen, C1 -4aliphatic, alkoxycarbonyl, (un) substituted
phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono-
or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl,
dialkylaminoalkyl, phenylatninocarbonyl, and (N-
heterocyclyl)carbonyl. Examples of such preferred R2
substituents include methyl, cyclopropyl, ethyl,
isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H,
CO2CH3/ CH20H, CH2OCH3/ CH2CH2CH2OH, C352C3l2CH2OCH3,
CH2CH2CH2OCH2Phf CH2CH2CH2NH2, CH2CH2CH2NHCOOC(CH3) 3/
CONHCH(CH3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, CONHCH2Ph,

CONH(cyclohexyl) , CON(Et)2, CON(CH3) CH2Ph, CONH (n-C3H7) ,
CON(Et)CH2CH2CH3, CONHCH2CH (CH3)2, CON(n-C3H7) 2/ CO(3-
methoxymetliylpyrrolidin-1 -yl) , CONH (3 -tolyl), CONH (4 -
tolyl) , CONHCH3/ CO(morpholin-l-yl) , CO (4-methylpiperazin-
1-yl) , CONHCH2CH2OH, CONH2, and CO(piperidin-l-yl) .
When the R2 and R2' groups of formula III are
taken together to form a ring, preferred R2/R2' ring,
systems containing the pyrazole ring include benzo,
pyrido, pyrimido, 3-oxo-2H-pyridazino, and a partially
unsaturated 6-membered carbocyclo ring. Examples of such
preferred R2/R2' ring systems containing the pyrazole ring
include the following:

Preferred substituents on the R2/R2' fused ring
of formula III include one or more of the following:
-halo, -N(R4)2, -C1 alkyl, -Ca_4 haloalkyl, -N02/ -0(d-4
alkyl) , -CO2(C1-4 alkyl) , -CN, - SO2 (C1_4 alkyl) , -SO2NH2,
-OC(O)NH2/ -NH2SO2(C1_4 alkyl) , -NHC(O) (C1-4 alkyl) ,
-C(O)NH2/ and -CO(C1-4 alkyl) , wherein the (d-4 alkyl) is a
straight, branched, or cyclic alkyl group. Preferably,
the (C1_4 alkyl) group is methyl.
Preferred formula III compounds have one or
more, and more preferably all, of the features selected
from the group consisting of:

(a) Ring b is an optionally substituted ring
selected from a phenyl, pyridinyl, piperidinyl,
piperazinyl, pyrrolidinyl, thienyl, azepanyl,
morpholinyl, 1,2,3,4-tetrahydroisoguinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3-dihydro-lff-isoindolyl, 2,3-
dihydro-lff-indolyl, isoquinolinyl, quinolinyl, or
naphthyl ring;
(b) Rx and Ry are taken together with their
intervening atoms to form an optionally substituted benzo
ring or a 5-7 membered carbocyclo ring; and
(c) R2' is hydrogen or methyl and R2 is T-W-R6 or
R, wherein W is -C(R6)2O-, -C(R6) 2N(R6) -, -CO-, -C02-,
-C(R6)OC(O)-, -C(R6)2N(R6)CO-, -C (R6)2N (R6) C (O) 0-, or
-CON(R6)-, and R is an optionally substituted group
selected from C1-6 aliphatic or phenyl, or R2 and R2' are
taken together with their intervening atoms to form a
substituted or unsubstitutedbenzo, pyrido, pyrimido, or
partially unsaturated 6-membered carbocyclo ring.
More preferred compounds of formula III have
one or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring D is an optionally substituted ring
selected from phenyl, pyridinyl, piperidinyl,
piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroguinolinyl,
2,3-dihydro-lH-isoindolyl, 2,3-dihydro-lH-indolyl,
isoquinolinyl, quinolinyl, or naphthyl;
(b) RX and Ry are taken together with their
intervening atoms to form a benzo ring or a 5-7 membered
carbocyclo ring optionally substituted with -R, oxo-,
halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R,
-SO2R, -SR, -N(R4)2/ -CON(R4)2, -SO2N(R4)2, -OC(=O)R,
-N(R4)COR, -N(R4)CO2 (optionally substituted Cx.6 aliphatic) ,
(a)
-N(R4)N(R4)2, -C=NN(R4)2/ -C=N-OR, -N(R4) CON(R4)2/
-N (c) each R5 is independently selected from halo,
oxo, CN, NO2/ -N(R4)2, -CO2R, -CONH(R4) , -N(R4)COR,
-SO2N(R4)2/ -N(R4)SO2R, -SR, -OR, -C(O)R, or a substituted
or unsubstituted group selected from 5-6 membered
heterocyclyl, C6-10 aryl, or C1-6 aliphatic.
Even more preferred compounds of formula III
have one or more, and more preferably all, of the
features selected from the group consisting of:
(a) Rx and Ry are taken together with their
intervening atoms to form a benzo or 6-membered partially
unsaturated carbocyclo ring optionally substituted with
halo, CN, oxo, C1_6 alkyl, Cx-e alkoxy, (C1-6 alkyl) carbonyl,
(C1-6 alkyl) sulfonyl, mono- or dialkylamino, mono- or
dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy,
or 5-6 membered heteroaryl;
(b) each R5 is independently selected from
-halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a
substituted or unsubstituted group selected from 5-6
membered heterocyclyl, C6-i0 aryl, or Ca_6 aliphatic; and
(c) R2' is hydrogen and R2 is selected from R2'
is hydrogen or methyl and R2 is T-W-R6 or R, wherein W is
-C(R6)2O-, -C(R6)2N(R6)-, -CO-, -CO2-, -C (R6) OC (0)-,
-C(R6)2N(R€)CO-, or -CON(R6)-, and R is an optionally
substituted group selected from C1_6 aliphatic or phenyl,
or R2 and R2' are taken together with their intervening
atoms to form a benzo, pyrido, or partially unsaturated
6-membered carbocyclo ring optionally substituted with
-halo, -N(R4)2, -C1-4 alkyl, -d-4 haloalkyl, -N02, -O(C1-4
alkyl), -CO2(d-4 alkyl) , -CN, -S02 (C1-4 alkyl), -SO2NH2,'
-OC(O)NH2, -NH2SO2(C1-4 alkyl) , -NHC(0) (C1-4 alkyl),

-C(0)NH2, or -CO(C1-4 alkyl), wherein the (C1-4 alkyl) is a
straight, branched, or cyclic alkyl group.
Representative compounds of formula III are set
forth in Table 2 below.

In another embodiment, this invention provides
a composition comprising a compound of formula III and a
pharmaceutically acceptable carrier.
One aspect of this invention relates to a
method of inhibiting GSK-3 activity in a patient,
comprising administering to the patient -a therapeutically
effective amount of a composition comprising a compound
of formula III.
Another aspect relates to a method of treating
a disea.se that is alleviated by treatment with a GSK-3
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula III.
Another aspect relates to a method of enhancing
glycogen synthesis and/or lowering blood levels of
glucose in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
III. This method is especially useful for diabetic
patients.
Another aspect relates to a method of
inhibiting the production of hyperphosphorylated Tau
protein in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
III. This method is especially useful in halting or
slowing the progression of Alzheimer's disease.
Another aspect relates to a method of
inhibiting the phosphorylation of ?-catenin in a patient
in need thereof, comprising administering to said patient
a therapeutically effective amount of a composition

comprising a compound of formula III. This method is
especially useful for treating schizophrenia.
One aspect of this invention relates to a
method of inhibiting Aurora activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula III.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with an Aurora
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula III. This method is
especially useful for treating cancer, such as colon,
ovarian, and breast cancer.
One aspect of this invention relates to a
method of inhibiting CDK-2 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula III.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a CDK-2
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of- a composition
comprising a compound of formula III. • This method is
especially useful for treating cancer, Alzheimer's
disease, restenosis, angiogenesis, glomerulonephritis,
cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis,
alopecia, and autoimmune diseases such as rheumatoid
arthritis.
One aspect of this invention relates to a
method of inhibiting Src activity in a patient,

comprising administering to the patient a therapeutically
effective amount, of a composition comprising a compound
of formula III.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a Src
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula III. This method is
especially useful for treating hypercalcemia,
osteoporosis, osteoarthritis, cancer, symptomatic
treatment of bone metastasis, and Paget's disease.
Another method relates to inhibiting GSK-3,
Aurora, CDK-2, or Src activity in a biological sample,
which method comprises contacting the biological sample
with, the GSK-3, Aurora, CDK-2, or Src inhibitor of
formula III, or a pharmaceutical composition thereof, in
an amount effective to inhibit GSK-3, Aurora, CDK-2, or
Src.
Each of the aforementioned methods directed to
the inhibition of GSK-3, Aurora, CDK-2, or Src, or the
treatment of a disease alleviated thereby, is preferably
carried out with a preferred compound of formula III, as
described above.
Compounds of formula III, wherein R2' is
hydrogen and RX and Ry are taken together with the
pyrimidine ring to form an optionally substituted
guinazoline ring system, are also inhibitors of ERK-2 and
AKT protein kinases.
Accordingly, another method of this invention
relates to a method of inhibiting ERK-2 or AKT activity
in a patient, comprising administering to the patient a
therapeutically effective amount of a composition

comprising a compound of formula III, wherein R2 is
hydrogen and Rx and Ry are taken together with the
pyrimidine ring to form an optionally substituted
quinazoline ring system.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a ERK-2 or
AKT inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula III, wherein R2' is
hydrogen and Rx and Ry are taken together with the
pyrimidine ring to form an optionally substituted
quinazoline ring system. This method is especially
useful for treating cancer,, stroke, hepatomegaly,
cardiovascular disease, Alzheimer's disease, cystic
fibrosis, viral disease, autoimmune diseases, restenosis,
psoriasis, allergic disorders including asthma,
inflammation, and neurological disorders.
Another embodiment of this invention relates to
compounds of formula IV:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or

heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or
heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;
Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 1-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any.substitutable
carbon on said fused ring is optionally and
independently substituted by T-R3, and any
substitutable nitrogen on said ring is substituted by
R4;
T is a valence bond or a C1_4 alkylidene chain;
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring containing 0-3 ring
heteroatoms selected from nitrogen, oxygen, or sulfur,
wherein said fused ring is optionally substituted by up
to three groups independently selected from halo, oxo,
-CN, -NO2, -R7, or -V-R6;
R3 is selected from -R, -halo, =0, -OR, -C(=O)R, -C02R,
-COCOR, -COCH2COR, -NO2/ -CN, -S(O)R, -S(O)2R, -SR,
-N(R4)2, -C0N(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)C0R,
-N(R4)C02 (optionally substituted C1-6 aliphatic) ,
-N(R4)N(R4)2, -C=NN(R4)2, -ON-QR, -N(R4) C0N(R4) 2,
-N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1_6

aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1_6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR,
-N(R4)2, -CON(R4)2/ -SO2N(R4)2, -OC(=O)R, -N(R4)C0R,
-N(R4)CO2 (optionally substituted C1_6 aliphatic),
-N(R4)N(R4)2/ -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4)2,
-N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2;
V is -O-, -S-, -SO-, -S02-, -N(R6)SO2-, -SO2N(R6)-,
-N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N (R6) C (O) O-,
-N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(RG) N(R6) -,
-C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(Re)2S-,
-C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C (R6) 2N(R6) - ,
-C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN(R6) - ,
-C(R6)=N-O-, -C(R6)2N(R6)N(RG)-, -C (R6) 2N(R6) SO2N(R6)-, or
-C (R€) 2N (R6) CON (R€) - ;
W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-,
-C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-,
-C(R6)OC(O)-, -C(R6)OC(O)N(R€)-, -C (R6) 2N(R6) CO-,
-C(R6)2N(R6)C(O)O-, -C(R6)=NN(R6)-, -C (R6) =N-O-,
-C (R6) 2N (R6) N (R6) -, -C (R6) 2N (R6) S02N (R6) - ,
-C(R6)2N(R6)CON(RS)-, or -CON(R6)-;
each R6 is independently selected from hydrogen or an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring; and

each R7 is independently selected from hydrogen or an
optionally substituted C1-G aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl ring or
heteroaryl.
Preferred formula IV Ring D monocyclic rings
include substituted and unsubstituted phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, thienyl,
azepanyl, and morpholinyl rings. Preferred formula IV
Ring D bicyclic rings include 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl,
2,3-dihydro-lH-isoindolyl, 2, 3-dihydro-lH-indolyl,
isoquinolinyl, quinolinyl, and naphthyl. Examples of
more preferred Ring D bicyclic rings include naphthyl and
isoquinolinyl.
Preferred substituents on Ring D of formula IV
include halo, oxo, CN, -NO2, -N(R4)2, -C02R, -CONH(R4) ,
-N(R4)COR, -SO2:N(R*)2, -N{R4)SO2R, -SR, -OR, -C(O)R, or
substituted or unsubstituted group selected from 5-6
membered heterocyclyl, C6-io &ryl, or Cx-6 aliphatic. More
preferred Rs substituents include -halo, -CN, -oxo, -SR,
-OR, -N(R4)2, -C(O)R, or a substituted or unsubstituted
group selected from 5-6 membered heterocyclyl, C6-10 aryl,
or C1-6 aliphatic. Examples of Ring D substituents
include -OH, phenyl, methyl, CH2OH, CH2CH2OH,
pyrrolidinyl, OPh, CF3, GsCH, Cl, Br, F, I, NH2, C(O)CH3,
i-propyl, tert-butyl, SEt, OMe, N(Me)2, methylene dioxy,
and ethylene dioxy.
When the Rx and Ry groups of formula IV are
taken together to form a fused ring, preferred RX/RY rings
include a 5-, 6-, 7-, or 8-membered unsaturated or
partially unsaturated ring having 1-2 heteroatoms. This •
provides a bicyclic ring system containing the pyrimidine

ring. Examples of preferred pyrimidine ring systems of
formula IV are the mono- and bicyclic systems shown
below.

More preferred pyrimidine ring systems of
formula IV include IV-E, IV-G, IV-H, IV-J, IV-K, rv-L,
IV-M, rv-T, and IV-U.
In the monocyclic pyrimidine ring system of
formula IV, preferred Rx groups include hydrogen, amino,
nitro, alkyl- or dialkylamino, acetamido, or a C1-4
aliphatic group such as methyl, ethyl, cyclopropyl,
isopropyl or t-butyl. preferred Ry groups include T-R3
wherein T is a valence bond or a methylene, and R3 is -R,

-N(R4)2, or -OR. When R3 is -R or -OR, a preferred R is
an optionally substituted group selected from C1-6
aliphatic, phenyl, or a 5-6 membered heteroaryl or
heterocyclyl ring. . Examples of preferred Ry groups
include 2-pyridyl, 4-pyridyl, piperidinyl, methyl, ethyl,
cyclopropyl, isopropyl, t-butyl, alkyl- or dialkylamino,
acetamido, optionally substituted phenyl such as phenyl,
methoxyphenyl, trimethoxyphenyl, or halo-substituted
phenyl, and methoxymethyl.
In the bicyclic pyrimidine ring system of
formula IV, the. ring formed when RX and Ry are taken
together may be substituted or unsubstituted. Suitable
substituents include -R, halo, -OR, -C(=o)R, -co2R,
-COCOR, -N02f -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -C0N(R4)2,
-SO2N(R4}2, -OC(=O)R, -N(R4)COR, -N(R4) C02 (optionally
substituted C1-6 aliphatic), -N(R4)N(R4)2, -C=NN(R4)2,
-C=N-OR, -N(R4)CON(R4)2, -N(R4} SO2N(R4)2, -N(R4)SO2R, or
-OC(=O)N(R4)2, wherein R and R4 are as defined above for
compounds of formula IV. Preferred Rx/Ry ring
substituents include -halo, -R, -OR, -COR, -CO2R,
-CON(R4)2/ -CN, or -N(R4)2 wherein R is a substituted or
unsubstituted C1_s aliphatic group.
The R2 and R2' groups of formula IV may be taken
together to form a fused ring, thus providing a bicyclic
ring system containing a pyrazole ring. Preferred fused
rings include benzo, pyrido, pyrimido, and a partially
unsaturated 6-membered carbocyclo ring. These are
exemplified in the following formula IV compounds having
a pyrazole-containing bicyclic ring system:

Preferred substituents on the R /R fused ring
of formula IV include one or more of the following:
-halo, -N(R4)2, -C1-4 alkyl, -C1-4 haloalkyl, -N02/ -O(CC1_4
alkyl) , -CO2(C1-4 alkyl) , -CN, -S02 (C1-4 alkyl), -SO2NH2,
-OC(O)NH2, -NH2SO2(C1-4 alkyl) , -NHC(O) (C3.-4 alkyl) ,
-C(O)NH2, and - CO (C1-4 alkyl) , wherein the (C1_4 alkyl) is a
straight, branched, or cyclic alkyl group. Preferably,
the (C1-4 alkyl) group is methyl.
When the pyrazole ring system of formula IV is
monocyclic, preferred R2 groups include hydrogen, a
substituted or unsubstituted group selected from aryl,
heteroaryl, or a C1 -6 aliphatic group. Examples of such
preferred R2 groups include methyl, t-butyl, -CH2OCH3,
cyclopropyl, furanyl, thienyl, and phenyl. A preferred
R2' group is hydrogen.
Preferred formula IV compounds have one or
more, and more preferably all, of the features selected
from the group consisting of:
(a) Ring D is an optionally substituted ring
selected from a phenyl, pyridinyl, piperidinyl,
piperazinyl, pyrrolidinyl, thienyl, azepanyl,
morpholinyl, 1,2,3,4- tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3-dihydro-IS-isoindolyl, 2,3-
dihydro-lff-indolyl, isoquinolinyl, quinolinyl, or
naphthyl ring;

(b) Rx is hydrogen or C3.-4 aliphatic and Ry is T-
R3, or Rx and Ry are taken together with their intervening
atoms to form an. optionally substituted 5-7. metobered
unsaturated or partially unsaturated ring having 1-2 ring
heteroatoms; and
(c) R2' is hydrogen or methyl and R2 is T-W-Rs or
R, wherein W is -C(Rs)jO-, -C(Rfi) 2N(R6) -, -CO-, -C02-,
-C(R6)OC(O)-, -C(R6)2N{R6)CO-, -C (R6)2N(R6) C (O) O-, or
-CON(R6)-, and R is an optionally substituted group
selected from C1-6 aliphatic or phenyl, or R2 and R2' are
taken together with their intervening atoms to form a
substituted or unsubstituted benzo, pyrido, pyrimido, or
partially unsaturated 6-membered carbocyclo ring.
More preferred compounds of formula IV have one
or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring D is an optionally substituted ring
selected from phenyl, pyridinyl, piperidinyl,
piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-
tetrahydroisoguinolinyl, 1,2,3,4-tetrahydroquinolinyl,
2,3- dihydro - Iff- i soindolyl, 2,3- dihydro - Iff- indolyl,
isoquinolinyl, quinolinyl, or naphthyl;
(b) Rx is hydrogen or methyl and Ry is -R,
N(R4)2/ or -OR, or Rx and Ry are taken together with their
intervening atoms to form a 5-7 membered unsaturated or
partially unsaturated ring having- 1-2 ring nitrogens,
wherein said ring is optionally substituted with -R,
halo, oxo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R,
-SO2R, -SR, -N(R4)2, -C0N(R4)2 -SO2N(R4}2, -OC(=O)R,
-N(R4)C0R, -N(R4)CO2 (optionally substituted C1-6 aliphatic) ,
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2,
-N(R4)SO2N(R4)2/ -N(R4)SO2R, or -OC (=O)N(R4) 2; and

(c) each R5 is independently selected from halo,
oxo, CN, N02, -N(R4)2, -CO2R, -C0NH(R4), -N{R4)COR,
-SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or a substituted
or unsubstituted group selected from 5-6 membered
heterocyclyl, C6-10 aryl, or C1-6 aliphatic.
Even more preferred compounds of formula IV
have one or more, and more preferably all, of the
features selected from the group consisting of:
(a) Rx and Ry are taken together with their
intervening atoms to form a 6-membered unsaturated or
partially unsaturated ring having 1-2 ring nitrogens,
optionally substituted with halo, CN, oxo, C1_6 alkyl, C1-6
alkoxy, (C1-6 alkyl) carbonyl, (C1-6 alkyl) sulfonyl, mono- or
dialkylamino, mono- or dialkylaminocarbonyl, mono- or
dialkylaminocarbonyloxy, or 5-6 membered heteroaryl;
(b) each R5 is independently selected from
-halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a
substituted or unsubstituted group selected from 5-6
membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic; and
(c) R2' is hydrogen and R2 is T-W-R6 or R,
wherein W is -C(R6)2O-, -C(R6)2N(R6)-, -CO-, -C02-,
-C(R6)OC(O)-, -C(R6)2N(R6)CO-, or -CON(R6)-, and R is an
optionally substituted group selected from C1-6 aliphatic
or phenyl, or R2 and R2' are taken together with their
intervening atoms to form a benzo, pyrido, or partially
unsaturated 6-membered carbocyclo ring optionally
substituted with -halo, oxo, -N(R4)2, -C1-4 alkyl, -C1-4
haloalkyl, -N02, -O(C1 alkyl) , -C02 (C1-4 alkyl), -CN,
-SO2(C1-4 alkyl) , -SO2NH2, -0C(0)NH2, -NH2SO2 (C1-4 alkyl) ,
-NHC(O) (C1-4 alkyl) , -C(o)NH2, or -CO(C1-4 alkyl) , wherein
the (C1-4 alkyl) is a straight, branched, or cyclic alkyl
group.
(a)

In another embodiment, this invention provides
a composition comprising a compound of; formula IV and a
pharmaceutically acceptable carrier.
One aspect of this invention relates to a
method of inhibiting GSK-3 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula IV.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a GSK-3
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a

therapeutically effective amount of a composition
comprising a compound of formula IV.
Another aspect relates to a method of enhancing
glycogen synthesis and/or lowering blood levels of
glucose in a patient in need thereof, comprising
administering to said patient a therapeutic ally effective
amount of a composition comprising a compound of formula
XV. This method is especially useful for diabetic
patients.
Another aspect relates to a method of
inhibiting the production of hyperphosphorylated Tau
protein in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
IV. This method is especially useful in halting or
slowing the progression of Alzheimer's disease.
Another aspect relates to a method of
inhibiting the phosphorylation of p-catenin in a patient
in need thereof, comprising administering to said patient
a therapeutically effective amount of a composition
comprising a compound of formula IV. This method is
especially useful for treating schizophrenia.
One aspect of this invention relates to a
method of inhibiting Aurora activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula IV.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with an Aurora
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula IV. This method is

especially useful for treating cancer, such as colon,
ovarian, and breast cancer.
One aspect of this invention relates to a
method of inhibiting CDK-2 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula IV.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a CDK-2
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula IV. This method is
especially useful for treating cancer, Alzheimer's
disease, restenosis, angiogenesis, glomerulonephritis,
cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis,
alopecia, and autoimmune diseases such as rheumatoid
arthritis.
Another method relates to inhibiting GSK-3,
Aurora, or CDK-2 activity in a biological sample, which
method comprises contacting the biological sample with
the GSK-3 or Aurora inhibitor of formula IV, or a
pharmaceutical composition thereof, in an amount
effective to inhibit GSK-3, Aurora or CDK-2.
Each of the aforementioned methods directed to
the inhibition of GSK-3, Aurora or CDK-2, or the
treatment of a disease alleviated thereby, is preferably
carried out with a preferred compound of formula IV, as
described above.
Another embodiment of this invention relates to
compounds of formula V:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
Z1 is N, CRa, or OR and Z2 is H or CH, provided that one
of Z1 and Z2 is nitrogen;
G is Ring C or Ring D;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -RB;
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or

heteroaryl ring, -R5 is hydrogen at each, ortho carbon
position of Ring D;
R1 is selected from -halo, -CN, -N02; T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1_6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R8, said C1-6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or R1
and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
substituted by oxo or T-R3, and any substitutable
nitrogen on said ring formed by RX and Ry is
substituted by R4;
T is a valence bond or a C1_4 alkylidene chain;
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -NO2/ -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -NO2, -CN, -S(O)R, -S(O)2R, -SR,
-N(R4)2, -CON(R7)2, -S02N(R7)2, -OC(=O)R, -N(R7)COR,

-N(R7)CO2 (optionally substituted C1-6 aliphatic) ,
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R7) CON(R7)2,
-N(R7)SO2N(R7)2, -N(R4)SO2R, or -OC (=O)N(R7) 2;
each R is independently selected from hydrogen or an
optionally substituted gxoup selected from C1_6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR,
-N(R4)2, -CON(R4)2/ -SO2N(R4)2, -OC(=O)R, -N(R4)COR,
-N(R4)CO2 (optionally substituted C1-6 aliphatic)
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R4) CON (R4) 2/
-N(R4)SO2N(R4)2 -N(R4)SO2R, or -OC (=O)N(R4) 2 or R5 and
an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
V is -O-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(R6)-,
-N(R6)-, -CO-, -CO2-, -N(R6)CO-, -N (R6) C (O) O-,
-N(R6)CON(R6)-, -N(RG)SO2N(R6)-, -N(R6) N(R6) - ,
-C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-/ -C(R6)2S-,
-C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C(R6) 2N (R6) - ,
-C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN (R6) - ,
-C(R6)=N-O-, -C(R6)2N(RG)N(R6)-, -C (R6) 2N(R6) SO2N(R6) - , or
-C(R6)2N(R6)CON(R6)-;
W is -C(R6)2O-, -C(R€)2S-, -C(R6)2SO-, -C(R6)2SO2-7
-C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-,
-C(Re)OC(O)-, -C(R6)OC(O)N(R6)-, -C (R6) 2N(Re) CO-,
-C(R6)2N(R6)C(O)O-, -C(R6)=NN(R6)-, -C(R6)=N-O-,

-C(R6)2N(R6)N(R6)-, -C(R6)2N(R6)SO2N(R6)-,
-C(R6)2N(R6)CON(R6)-, or -CON(R6)-;
each R6 is independently selected from hydrogen, an
optionally substituted C1_4 aliphatic group, or two RG
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1_6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R8 is independently selected from an optionally
substituted C1-4 aliphatic group, -OR6, -SR6, -COR6,
-SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -NO2, -CON(R6)2, or
-CO2R6; and
Ra is selected from halo, -OR, -C(=O)R, -C02R, -COCOR,
-N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2,
-SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) CO2 (optionally
substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2,
-C=N-OR, -N(R4)CON(R4)2, -N(R4) SO2N(R4) 2, -N(R4)SO2R,
-OC(=O)N(R4)2, or an optionally substituted group
selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl
ring having 5-10 ring atoms, or a heterocyclyl ring
having 5-10 ring atoms.
Compounds of formula V may be represented by
specifying Z1 and Z2 as shown below:

When the Rx and Ry groups of formula V are taken
together to form a fused ring, preferred Rx/Ry rings
include a 5-, S-, 1-, or 8-tnembered unsaturated or
partially unsaturated ring having 0-2 heteroatoms,
wherein said Rx/Ry ring is optionally substituted. This
provides a bicyclic ring system containing a pyridine
ring. Examples of preferred bicyclic ring systems of
formula V are shown below.

More preferred bicyclic ring systems of formula
V include Va-A, Vb-A, Vc-A, Va-B, Vb-B, Vc-B, Va-D, Vb-D,
Vc-D, Va-E, Vb-E, Vc-E, Va-J, Vb-J, Vc-J, Va-K, Vb-K,
Vc-K, Va-L, Vb-L, Vc-L, Va-M, Vb-M, and Vc-M, most
preferably Va-A, Vb-A, Ve-A, Va-B, Vb-B, and Vc-B.
In the monocyclic pyridine ring system of
formula V, preferred RX groups include hydrogen, alkyl- or
dialkylamino, acetamido, or a C1_4 aliphatic group such as
methyl, ethyl, cyclopropyl, isopropyl or t-butyl.
Preferred Ry groups include T-R3 wherein T is a valence
bond or a methylene, and R3 is -R, -N(R4)2/ or -OR. When
R3 is -R or -OR, a preferred R is an optionally
substituted group selected from C1-e aliphatic, phenyl, or
a 5-6 membered heteroaryl or heterocyclyl ring. Examples
of preferred Ry include 2-pyridyl, 4-pyridyl, piperidinyl,
methyl, ethyl, cyclopropyl, isopropyl, t-butyl, alley 1- or
dialkylamino, acetamido, optionally substituted phenyl
such as phenyl or halo-substituted phenyl, and
methoxymethyl.
In the bicyclic ring system of formula V, the
ring formed when RX and Ry are taken together may be
substituted or unsubstituted. Suitable substituents
include -R, halo, -OR, -C(=O)R, -CO2R, -C0COR, -N02, -CN,
-S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2,
-OC(=o)R, -N(R4)C0R, -N(R4)CO2 (optionally substituted C1-6
aliphatic), -N(R4)N(R4)2/ -C=NN(R4)2/ -ON-OR,
-N(R4)CON(R4)2, -N(R4)SO2N(R4)2/ -N(R4)SO2R, or

-OC(=O)N(R4)2, wherein R and R4 are as defined above.
Preferred Rx/Ry ring substituents include -halo, -R, -OR,
-COR, -CO2R, -CON(R4)2, -CN, or -N(R4)2 wherein R is an
optionally substituted C1-6 aliphatic group.
The R2 and R2' groups of formula V may be taken
together to form a fused ring, thus providing a bicyclic
ring system containing a pyrazole ring. Preferred fused
rings include benzo, pyrido, pyrimido, and a partially
unsaturated 6-membered carbocyclo ring. These are
exemplified in the following formula V compounds having a
pyrazole-containing bicyclic ring system:

Preferred substituents on the R2/R2' fused ring
of formula V include one or more of the following: -halo,
-N(R4)2, -C1-4 alkyl, -QL-4 haloalkyl, -N02/ -0(C1_4 alkyl) ,
-CO2(C1-4 alkyl) , -C3N, -SO2(d_4 alkyl) , -SO2NH2, -OC(O)NH2,
-NH2SO2(C1-4 alkyl) , -NHC(O) (d.4 alkyl) , -C(O)NH2/ and
-CO (C2-4 alkyl), wherein the (C1 alkyl) is a straight,
branched, or cyclic alkyl group. Preferably, the (Ca-4
alkyl) group is methyl.
When the pyrazole ring system is monocyclic,
preferred R2 groups include hydrogen, C1_4 aliphatic,
alkoxycarbonyl, (un) substituted phenyl, hydroxyalkyl,
alkoxyalkyl, aminocarbonyl, mono- or
dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl,
dialkylaminoalkyl, phenylaminocarbonyl, and (N-

heterocyclyl)carbonyl. Examples of such preferred R2
substituents include methyl, cyclopropyl, ethyl,
isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H,
CO2CH3/ CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3,
CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC (CH3)3,
CONHCH(CH3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, CONHCH2Ph,
CONH (cyclohexyl) , CON (Et) 2, CON (CH3) CH2Ph, CONH (n-C3H7) ,
CON(Et)CH2CH2CH3, CONHCH2CH (CH3) 2, CON (n-C3H7) 2, C0(3-
methoxymethylpyrrolidin-1-yl), CONH (3 - tolyl) , CONH (4 -
tolyl) , CONHCH3, CO (morpholin-1-yl) , C0(4-methylpiperazin-
1-yl) , CONHCH2CH2OH, CONH2, and CO (piperidin-1-yl) . A
preferred R2' group is hydrogen.
More preferred ring systems of formula V are
the following, which may be substituted as described
above, wherein R2 and R2' are taken together with the
pyrazole ring to form an optionally substituted indazole
ring; and Rx and Ry are each methyl, or Rx and Ry are taken
together with the pyridine ring to form an optionally
substituted quinoline, isoguinoline, tetrahydroquinoline
or tetrahydroisoquinoline ring:

When G is Ring C, preferred formula V Ring C
groups are phenyl and pyridinyl. When two adjacent
substituents on Ring C are taken together to form a fused
ring, Ring C is contained in a bicyclic ring system.
Preferred fused rings include a benzo or pyrido ring.

Such rings preferably are fused at ortho and meta
positions of Ring C. Examples of preferred bicyclic Ring
C systems include napbthyl and isoquinolinyl. Preferred
R1 groups include -halo, an optionally substituted Ci-6
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2,
-N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6.
When R1 is an optionally substituted c1-6 aliphatic group,
the most preferred optional substituents are halogen.
Examples of preferred R1 groups include -CF3, -Cl, -F,
-CN, -COCH3, -OCH3, -OH, -CH2CH3/ -OCH2CH3, -CH3, -CF2CH3,
cyclohexyl, t-butyl, isopropyl, cyclopropyl, -CsCH,
-CsC-CH3, -SO2CH3, -SO2NH2, -N(CH3)2, -CO2CH3, -CONH2,
-NHCOCH3, -0C(0)NH2, -NHSO2CH3/ and -OCF3.
On Ring C preferred R5 substituents, when
present, include -halo, -CN, -N02, -N(R4)2, optionally
substituted Cx.6 aliphatic group, -OR, -C(O)R, -CO2R,
-CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4)SO2R. More
preferred R5 substituents include -Cl, -F, -CN, -CF3,
-NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2 -0(C1_4
aliphatic), C1_4 aliphatic, and -CO2(Ci_4 aliphatic).
Examples of such preferred R5 substituents include -Cl,
-F, -CN, -CF3, -NH2/ -NHMe7 -NMe2/ -OEt, methyl, ethyl,
cyclopropyl, isopropyl, t-butyl, and -CO2Et.
When G is Ring D, preferred formula V Ring D
monocyclic rings include substituted and unsubstituted
phenyl, pyridinyl, piperidinyl, piperazinyl,
pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings.
When two adjacent substituents on Ring D are taken
together to form a fused ring, the Ring D system is
bicyclic. Preferred formula V Ring D bicyclic rings
include 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, quinolinyl, and

naphthyl. Examples of more preferred bicyclic Ring D
systems include naphthyl and isoguinolinyl.
Preferred substituents on Ring D of formula V
include one or more of the following: halo, oxo, CN, -N02,
-N(R4)2, -Co2R, -CONH(R4), -N(R4)C0R, -SO2N(R4)2, -N(R4)SO2R,
-SR, -OR, -C(O)R, or substituted or unsubstituted group
selected from 5-6 membered heterocyclyl, C6_10 aryl, or C1_6
aliphatic. More preferred Ring D substituents include
-halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a
substituted or unsubstituted group selected from 5-6
membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic.
Examples of Ring D substituents include -OH, phenyl,
methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, OsCH, Cl,
Br, F, I, NH2, C(O)CH3, i-propyl, tert-butyl, SEt, OMe,
N(Me)2; methylene dioxy, and ethylene dioxy.
Preferred formula V compounds have one or more,
and more preferably all, of the features selected from
the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from a
naphthyl, quinolinyl or isoquinolinyl ring, and R1 is
-halo, an optionally substituted C1_6 aliphatic group,
phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6,
-CONH2, -NHCOR6, -OC(O)NH2, or -NHS02R6; or Ring D is an
optionally substituted ring selected from a phenyl,
pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl,
thienyl, azepanyl, morpholinyl, 1,2,3,4-
tetrahydroisoguinolinyl, 1,2,3,4-tetrahydroguinolinyl,
2, 3 -dihydro-lH-isoindolyl, 2, 3-dihydro-lH-indolyl,
isoguinolinyl, quinolinyl, or naphthyl ring,-

(b) Rx is hydrogen or C1-4 aliphatic and Ry is T-
R3, or Rx and Ry are taken together with their intervening
atoms to form an optionally substituted 5-7 membered
unsaturated or partially unsaturated ring having 0-2 ring
nitrogens; and
(c) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl, .
heteroaryl, or a C1_6 aliphatic group, or R2 and R2' are
taken together with their intervening atoms to form a
substituted or unsubstituted benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring.
More preferred compounds of formula V have one
or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic
group, phenyl, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3- dihydro - 1H- isoindolyl, 2,3-
dihydro-lH-indolyl, isoguinolinyl, quinolinyl, or
naphthyl;
(b) Rx is hydrogen or methyl and Ry is -R,
N(R4)2, or -OR, or Rx and Ry are taken together with their
intervening atoms to form a benzo ring or a 5-7 membered
partially unsaturated carbocyclo ring, said benzo or
carbocyclo ring optionally substituted with -R, halo,
-OR, -C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R,
-SR, -N(R4)2, -CON(R4)2/ -SO2N(R4)2, -OC(=O)R, -N(R4)COR,

-N(R4)CO2 (optionally substituted C1-6 aliphatic) ,
-N(R4)N(R4)2/ -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2,
-N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4) 2;
(c) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl, or
a C1-6 aliphatic group, or R2 and R2' are taken together
with their intervening atoms to form a substituted or
unsubstituted benzo, pyrido, pyrimido or partially
unsaturated 6-membered carbocyclo ring; and
(d) Ring D is substituted by oxo or R5, wherein
each R5 is independently selected from -halo, -CN, -N02,
-N(R4)2, optionally substituted C1_6 aliphatic group, -OR,
-C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, or
-N(R4)SO2R.
Even more preferred compounds of formula V have
one or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1_4 aliphatic group optionally substituted
with halogen, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroguinolinyl, isoguinolinyl, quinolinyl, or
naphthyl;
(b) Rx is hydrogen or methyl and Ry is methyl,
methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl,
alkyl- or an optionally substituted group selected from
2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry
are taken together with their intervening atoms to form a

benzo ring or a 6-membered partially unsaturated
carbocyclo ring optionally substituted with halo, CN,
oxo, C1-6 alkyl, C1_6 alkoxy, (C1-6 alkyl) carbonyl, (C1_6
alkyl)sulfonyl, mono- or dialkylamino, mono- or
dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy,
or 5-6 metnbered heteroaryl;
(c) R2 and R2' are taken together with their
intervening atoms to form a benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring
optionally substituted with -halo, -N(R4)2 -C1-4 alkyl,
-C1-4 haloalkyl, -N02, -0(03.-4 alkyl) , -CO2(C1-4 alkyl) , -CN,
-SO2(C1_4 alkyl) , -SO2NH2, -OC(O)NH2, -NH2SO2 (Ca-4 alkyl) ,
-NHC(O) (C1.4 alkyl) , -C(O)NH2, or -CO (C1-4 alkyl) , wherein
the (C1-4 alkyl) is a straight, branched, or cyclic alkyl"
group; and
(d) Ring D is substituted by oxo or R5, wherein
each R5 is independently selected from -Cl, -F, -CN, -CF3,
-NH2, -NH(C1_4 aliphatic), -N(C1_4 aliphatic)2/ -O(C1-4
aliphatic), C1_4 aliphatic, and -C02(C1_4 aliphatic).
Representative compounds of formula V are set
forth in Table 4 below.

In another embodiment, this invention provides
a composition comprising a compound of formula V and a
pharmaceutically acceptable carrier.
One aspect of this invention relates to a
method of inhibiting GSK-3 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula V.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a GSK-3
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula V.
Another aspect relates to a method of enhancing
glycogen synthesis and/or lowering blood levels of
glucose in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprisinq- a compound of formula

V. This method is especially useful for diabetic
patients.
Another aspect relates to a method of
inhibiting the production of hyperphosphorylated Tau
protein in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
V. This method is especially useful in halting or
slowing the progression of Alzheimer's disease.
Another aspect relates to a method of
inhibiting the phosphorylation of P-catenin in a patient
in need thereof, comprising administering to said patient
a therapeutically effective amount of a composition
comprising a compound of formula V. This method is
especially useful for treating schizophrenia.
One aspect of this invention relates to a
method of inhibiting Aurora activity in a patient,
comprising administering to the.patient a therapeutically
effective amount of a composition comprising a compound
of formula V.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with an Aurora
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula V. This method is
especially useful for treating cancer, such as colon,
ovarian, and breast cancer.
One aspect of this invention relates to a
method of inhibiting CDK-2 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula V.

Another aspect relates to a method of treating
a disease that is alleviated by treatment with a CDK.-2
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula V. This method is
especially useful for treating cancer, Alzheimer's
disease, restenosis, angiogenesis, glomerulonephritis,
cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis,
alopecia, and autoimmune diseases such as rheumatoid
arthritis.
Another method relates to inhibiting GSK-3,
Aurora, or CDK-2 activity in a biological sample, which
method comprises contacting the biological sample with
the GSK-3 or Aurora inhibitor of formula V, or a
pharmaceutical composition thereof, in an amount
effective to inhibit GSK-3, Aurora or CDK-2.
Each of the aforementioned methods directed to
the inhibition of GSK-3, Aurora or CDK-2, or the
treatment of a disease alleviated thereby, is preferably
carried out with a preferred compound of formula V, as
described above.
Another embodiment of this invention relates to
compounds of formula VI:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
G is Ring C or Ring D;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8 ;
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or
heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;
R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R8, said C1-6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or R1

and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
Ry is T-R3';
T is a valence bond or a C1-4 alkylidene chain;
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4;
R3 is an optionally substituted group selected from C1-6
aliphatic, C3-10 carbocyclyl, C6-10 aryl, a heteroaryl
ring having 5-10 ring atoms, or a heterocyclyl ring
having 5-10 ring atoms;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1_6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each Rs is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR,
-N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)C0R,
-N(R4)CO2 (optionally substituted C1_6 aliphatic) ,
-N(R4)N(R4)2, -C=NN(R4)2/ -C=N-OR, -N(R4) CON (R4) 2/
-N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4) 2, or Rs and

an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
V is -0-, -S-, -SO-, -SO2-, -N(R6-N(R6) C (0) O- ,
-N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(R6)N(R6) -,
-C(O)N(R6)-, -OC(O)N(R6)-, -C(R6)2O-, -C(R6)2S-,
-C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N(R6)-, -C (R6) 2N(R6) - ,
-C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN(R6) - ,
-C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C(R6) 2N(R6) SO2N(R6) - , or
-C(R6)2N(R6)CON(R6) -;
W is -C(R6)2O-, -C(R6)2S-, -C(R6)2S0-, -C(R6)2SO2-,
-C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -C02-,
-C(R6)OC(O)-, -C(R6)OC(O)N(R6)-, -C (R6) 2N(R6) CO- ,
-C(R6)2N(R6)C(O)O-, -C(R6)=NN(R6)-, -C (R6) =N-O-,
-C(R6) 2N(R6)N(R6) - , -C (R6) 2N(R6) SO2N(R6) - ,
-C(R6)2N(R6)CON(R6)-, or -CON(R6)-;
each R6 is independently selected from hydrogen, an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1_6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring; and
each R8 is independently selected from an optionally
substituted C1_4 aliphatic group, -OR6, -SR6, -COR6,
-SO2R6, -N(RG)2, -N(RG)N{R6)2, -CN, -N02, -CON(R6)2, or
-CO2R6.
Preferred Ry groups of formula VI include T-R3
wherein T is a valence bond or a methylene, and R3' is an
optionally substituted group selected from C3.-6 aliphatic,

C3-10 carbocyclyl, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms. A preferred R3' group is an optionally substituted
group selected from C3_6 carbocyclyl, phenyl, or a 5-6
membered heteroaryl or heterocyclyl ring. Examples of
preferred Ry include 2-pyridyl, 4-pyridyl, piperidinyl,
morpholinyl, cyclopropyl, cyclohexyl, and optionally
substituted phenyl such as phenyl or halo-substituted
phenyl.
The R2 and R2' groups of formula VT may be taken
together to form a fused ring, thus providing a bicyclic
ring system containing a pyrazole ring. Preferred fused
rings include benzo, pyrido, pyrimido, and a partially
unsaturated 6-membered carbocyclo ring. These are
exemplified in the following formula VI compounds having
a pyrazole-containing bicyclic ring system:

Preferred substituents on the R2/R2' fused ring
include one or more of the following: -halo, -N(R4)2, -Ci_4
alkyl, -d-4 haloalkyl, -NO2, -O(d-4 alkyl) , -CO2(C1-4
alkyl) , -CN, -SO2(C1-4 alkyl) , -SO2NH2/ -OC(O)NH2,
-NH2SO2(Ca-4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(0)NH2, and
-C0(C1-4 alkyl), wherein the (C1 alkyl) is a straight,
branched, or cyclic alkyl group. Preferably, the (C1-4
alkyl) group is methyl.

When the pyrazole ring system is monocyclic>
preferred R2 groups of formula VI include hydrogen, C1-4
aliphatic, alkoxycarbonyl, (un)substituted phenyl,
hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or
dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl,
dialkylaminoalkyl, phenylaminocarbonyl, and (N-
heterocyclyDcarbonyl. Examples of such preferred R2
substituents include methyl, cyclopropyl, ethyl,
isopropyl, propyl, t-butyl, oyclopentyl, phenyl, CO2H,
CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3,
CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC (CH3) 3
CONHCH(CH3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, CONHCH2Ph,
CONH(cyclohexyl) , CON(Et)2, CON(CH3)CH2Ph, CONH(n-C3H7) ,
CON(Et)CH2CH2CH3, CONHCH2CH (CH3) 2,( CON(n-C3H7) 2, C0(3-
methoxymethylpyrrolidin-l-yl), CONH(3-tolyl), C0NH(4-
tolyl) , CONHCH3, CO(morpholin-l-yl) , C0(4-methylpiperazin-
1-yl), COMHCH2CH2OH, CONH2, and CO(piperidin-l-yl). A
preferred R2' group is hydrogen.
When G is Ring C, preferred formula VI Ring C
groups are phenyl and pyridinyl. When two adjacent
substituents on Ring C are taken together to form a fused
ring, Ring C is contained in a bicyclic ring system.
Preferred fused rings include a benzo or pyrido ring.
Such rings preferably are fused at ortho and meta
positions of Ring C. Examples of preferred bicyclic Ring
C systems include naphthyl and isoquinolinyl. Preferred
R1 groups include -halo, an optionally substituted Ci-e
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2,
-N(R6)2, ,-CO2R6, -CONH2/ -NHCOR6, -OC(O)NH2, or -NHS02RG.
When R1 is an optionally substituted Ca-6 aliphatic group,
the most preferred optional substituents are halogen.
Examples of preferred R1 groups include -CF3, -Cl, -F,"
-CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2CH3, -CH3, -CF2CH3,

cyclohexyl, t-butyl, isopropyl, cyclopropyl, -C=CH,
-C=C-CH3, -SO2CH3, -SO2NH2, -N(CH3)2, -CO2CH3/ -CONH2,
-NHCOCH3/ -OC(O)NH2, -NHSO2CH3/ and -OCF3.
On Ring C preferred R5 substituents, when
present, include -halo, -CN, -N02/ -N(R4)2, optionally
substituted Cx-6 aliphatic group, -OR, -C(O)R, -CO2R,'
-CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4) SO2R. More
preferred R5 substituents include -Cl, -F, -CN, -CF3,
-NH2, -NH(CH2-4 aliphatic), -N(C1-4 aliphatic)2 -O(C1-4
aliphatic), C1-4 aliphatic, and -CO2(C1-4 aliphatic).
Examples of such preferred R5 substituents include -Cl,
-F, -CN, -CF3, -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl,
cyclopropyl, isopropyl, t-butyl, and -CO2Et.
When G is Ring D, preferred formula VI Ring D
monocyclic rings include substituted and unsubstituted
phenyl, pyridinyl, piperidinyl, piperazinyl,
pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings.
When two adjacent substituents on Ring D are taken
together to form a fused ring, the Ring D system is
bicyclic Preferred formula VT Ring D bicyclic rings
include 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3-dihydro- 1H- isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, guinolinyl, and
naphthyl. Examples of more preferred bicyclic Ring D
systems include naphthyl and isoquinolinyl.
Preferred substituents on formula VT Ring D
include one or more of the following: halo, oxo, CN, -N02,
-N(R4)2, -CO2R, -C0NH(R4), -N(R4)COR, -SO2N(R4)2/ -N(R4)SO2R,
-SR, -OR, -C(O)R, or substituted or unsubstituted group
selected from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6
aliphatic. More preferred Ring D substituents include
-halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a
substituted or unsubstituted group selected from 5-6

membered heterocyclyl, C6-10 aryl, or C1_6 aliphatic.
Examples of Ring D substituents include -OH, phenyl,
methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, C=CH, Cl,
Br, F, I, NH2, C(O)CH3, i-propyl, tert-butyl, SEt, OMe,
N(Me)2, methylene dioxy, and ethylene dioxy.
Preferred formula VI compounds have one or
more, and more preferably all, of the features selected
from the group consisting of:
(a) Ring C is selected from a phenyl or
pyridinyl ring, optionally substituted by -R5, wherein
when Ring C and two adjacent substituents thereon form a
bicyclic ring system, the bicyclic ring system is
selected from a naphthyl, quinolinyl or isoquinolinyl
ring, and R1 is -halo, an optionally substituted C1_6
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2,
-N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; or
Ring D is an optionally substituted ring selected from a
phenyl, pyridinyl, piperidinyl, piperazinyl,
pyrrolidinyl, thienyl, azepanyl, morpholinyl, 1,2,3,4-
tetrahydroisoguinolinyl, 1,2,3,4-tetrahydroquinolinyl,
2,3 -dihydro- 1H-isoindolyl, 2,3-dihydro- 1H-indolyl,
isoquinolinyl, quinolinyl, or naphthyl ring;
(b) Ry is T-R3', wherein T is a valence bond or
a methylene; and
(c) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl,
heteroaryl, or a C1_6 aliphatic group, or R2 and R2' are
taken together with their intervening atoms to form a
substituted or unsubstituted benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring.
More preferred compounds of formula VT have one
or more, and more preferably all, of the features
selected from the group consisting of:

(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1_6 haloaliphatic group, a C1_6 aliphatic
group, phenyl, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisbguinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3- dihydro- 1H- isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or
naphthyl;
(b) Ry is T-R3', wherein T is a valence bond or
a methylene and R3 is an optionally substituted group
selected from C1_6 aliphatic, C3-6 carbocyclyl, C6-10 aryl, a
heteroaryl- ring having 5-10 ring atoms, or a heterocyclyl
ring having 5-10 ring atoms;
(c) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl, or
a C1_6 aliphatic group, or R2 and R2' are taken together
with their intervening atoms to form a substituted or
unsubstituted benzo, pyrido, pyrimido or partially
unsaturated 6-membered carbocyclo ring; and
(d) Ring D is substituted by oxo or R5, wherein
each R5 is independently selected from -halo, -CN, -NO2,
-N(R4)2, optionally substituted C1-6 aliphatic group, -OR,
-C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, or
-N(R4)S02R.
Even more preferred compounds of formula VI
have one or more, and more preferably all, of the
features selected from the group consisting of:
(a) Ry is T-R3', wherein T is a valence bond or
a methylene and R3' is an optionally substituted group

selected from C1-4 aliphatic, C3.6 carbocyclyl, phenyl, or
a 5-6 membered heteroaryl or heterocyclyl ring;
(b) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-4 aliphatic group optionally substituted
with halogen, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, isoquinolinyl, guinolinyl, or
naphthyl;
(c) R2 and R2' are taken together with their
intervening atoms to form a benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring
optionally substituted with -halo, -N(R4)2, -C1-4 alkyl,
-d-4 haloalkyl, -N02, -O(C1-4 alkyl) , -CO2(C1-4 alkyl) , -CN,
-SO2(C1-4 alkyl) , -SO2NH2, -0C(O)NH2, -NH2SO2(C1-4 alkyl) ,
-NHC(O) (C1_4 alkyl) , -C(O)NH2, or -CO (C1-4 alkyl) , wherein
the (C1-4 alkyl) is a straight, branched, or cyclic alkyl
group,- and
(d) Ring D is substituted by oxo or R5, wherein
each Rs is independently selected from -C1, -F, -CN, -CF3,
-NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -0(C1-4
aliphatic) , C1_4 aliphatic, and -CO2(C1-4 aliphatic).
Another embodiment of this invention relates to
compounds of formula VXa:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
G is Ring C or Ring D;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring CU are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8;
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or
heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;

R1 is selected from -halo, -CN, -N02, T-V-Re, phenyl, 5-6
membered heteroaryl ring, 5-6 menibered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R8, said C1_6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or R1
and an adjacent substituent taken together with their
intervening atoms _form said ring fused to Ring C;
T is a valence bond or a C1_4 alkylidene chain;
R2 and R2' are taken together with their intervening atoms
to form a fused, 5-8 membered, unsaturated or partially
unsaturated, ring having 0-3 ring heteroatoms selected
from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4 ;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R* on the same nitrogen are taken
together to form a 5-8. membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -N02, -CN, -S(O)R, -SO2R, -SR,
-N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR,
-N(R4)CO2 (optionally substituted C1-6 aliphatic) ,
-N(R4)N(R4)2/ -C=NN(R4)2, -C=N-OR, -N (R4) CON (R4)

-N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(-O)N(R4) 2, or Rs and
an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
V is -0-, -S-, -SO-, -S02-, -N(R6)SO2-# -SO2N(R6)-,
-N(R6)-, -CO-, -C02-, -N(R6)CO-, -N(RS) C(O) 0-,
-N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(R6)N(R6) -,
-C(O)N(R6)-, -OC(O)N(R6)-,' -C(R6)2O-, -C(R6)2S-,
-C(R6)2SO-, -C(R6)2SO2-, -C(RS)2SO2N(R6)-, -C (R6) 2N(R6)-,
-C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN (R6) - ,
-C(R6)=N-O-, -C(R6)2N{Re)N(R6)-, -C(R6) 2N(R6) SO2N(R6) - , or
-C(R6)2N(R6)CON(R6)-;
W is -C(R6)2O-, -C(R6)2S-, -C(R6)2S0-, -C(R6)2SO2-,
-C{R6)2SO2N(RS)-, -C(R6)2N(R6)-, -CO-, -C02-,
-C(R6)OC(O)-, -C(R6)OC(0)N(R6)-, -C (R6)2N(R6) CO-,
-C{R6)2N(R6)C(O)O-, -C(R6)=NN(R6)-, -C(R6)=N-O-,
-C(R6)2N(R6)N(R6)-, -C(R6)2N(R6)SO2N(R6)-,
-C(R6)2N(R6)CON(R6)-/ or -CON{R6)-;
each R6 is independently selected from hydrogen, an
optionally substituted C1-4 aliphatic group, or two Rs
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring; and
each R8 is independently selected from an optionally
substituted C1-4 aliphatic group, -OR6, -SR6, -COR6,
-SO2R6, -N(R6)2, -N(R6)N(R6)2, rCN, -N02, -CON(R6)2, or
-CO2R6.
Preferred rings formed by the R2 and R2' groups
of formula Via include benzo, pyrido, pyrimido, and a

partially unsaturated 6-membered carbocyclo ring. These
are exemplified in the following formula VIa compounds
having a pyrazole-containing bicyclic ring system:

Preferred substituents on the R2/R2 fused ring
include one or more of the following: -halo, -N(R4)2, -C1-4
alkyl, -C1.4 haloalkyl, -NO2, -O(C1-4 alkyl) , -CO2(C1_4
alkyl) , -CN, -S02 (C1-4 alkyl) , -SO2NH2, -OC(O)NH2,
-NH2SO2(C1.4 alkyl) , -NHC(O) (C1-4 alkyl) , -C(O)NH2, and
-CO(C1-4 alkyl), wherein the (C1-4 alkyl) is a straight,
branched, or cyclic alkyl group. Preferably, the (C1-4
alkyl) group is methyl.
When G is Ring C, preferred formula VIa Ring C
groups are phenyl and pyridinyl. When two adjacent
substituents on Ring C are taken together to form a fused
ring Ring C is contained in a bicyclic ring system.
Preferred fused rings include a benzo or pyrido ring.
Such rings preferably are fused at ortho and meta
positions of Ring C. Examples of preferred bicyclic Ring
C systems include naphthyl and isoquinolinyl. Preferred
R1 groups include -halo, an optionally substituted C1-6
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2,
-N(Rs)2, -CO2R6, -C0NH2, -NHCOR6, -0C(0)NH2, or -NHSO2R6.
When R1 is an optionally substituted C1-6 aliphatic group,
the most preferred optional substituents are halogen.
Examples of preferred R1 groups include -CF3, -C1, -F,

-CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2OCH3, -CH3, -CF2OCH3,
cyclohexyl, t-butyl, isopropyl, cyclopropyl, -CsCH,
-C=C-OCH3, -SO2CH3/ -SO2NH2, -N(CH3)2, -CO2CH3, -CONH2,
-NHCOCH3, -OC(O)NH2, -NHSO2CH3, and -OCF3.
On Ring C preferred Rs substituents, when
present, include -halo, -CN, -N02, -N(R4)2, optionally
substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R,
- CONH (R4) , -N (R4) COR, - SO2N (R4) 2, and -N (R4) SO2R. More
preferred R5 substituents include -Cl, -F, -CN, -CF3,
-NH2, -NH(OCH3.4 aliphatic) , -N(C1-4- aliphatic)2, -o(C1-4
aliphatic), C3..4 aliphatic, and -CO2(C1-4 aliphatic).
Examples of such preferred Rs substituents include -Cl,
-F, -CN, -CF3 -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl,
cyclopropyl, isopropyl, t-butyl, and -CO2Et.
When G is Ring D, preferred formula VIa Ring D
monocyclic rings include substituted and unsubstituted
phenyl, pyridinyl, piperidinyl, piperazinyl,
pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings.
When two adjacent substituents on Ring D are taken
together to form a fused ring, the Ring D system is
bicyclic. Preferred formula VIa Ring D bicyclic rings
include 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, quinolinyl, and
naphthyl. Examples of more preferred bicyclic Ring D
systems include naphthyl and isoquinolinyl.
Preferred substituents on the formula Via Ring
D include one or more of the following: halo, oxo, CN,
-N02, -N(R4)2, -CO2R, -CONH(R4), -N(R4)C0R, -SO2N(R4)2,
-N(R*)S02R, -SR, -OR, -C(0)R, or substituted or
unsubstituted group selected from 5-6 membered
heterocyclyl, C6-io axyl, or C1-6 aliphatic. More preferred
Ring D substituents include -halo, -CN, -oxo, -SR, -OR,

-N(R )2/ -C(O)R, or a substituted or unsubstituted group
selected from 5-6 membered heterocyclyl, C6-10 aryl, or C2.e
aliphatic. Examples of Ring D substituents include -OH,
phenyl, methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3,
OsCH, C1, Br, F, 2, NH2, C(O)CH3, i-propyl, tetr-butyl,
SEt, OMe, N(Me)2, methylene dioxy, and ethylene dioxy.
Preferred formula VIa compounds have one or
more, and more preferably all, of the features selected
from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from a
naphthyl, quinolinyl or. isoquinolinyl ring, and R1 is
-halo, an. optionally substituted C1_6 aliphatic group,
phenyl, -COR6, -OR6, -CN, -SO2R6, -SOaNH2, -N(K6)2, -CO2RS,
-CONH2, -NHCOR*, -OC{O)NH2, or -NHSO2R6; or Ring D is an
optionally substituted ring selected from a phenyl,
pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl,
thienyl, azepanyl, morpholinyl, 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroguinolinyl,
2,3-dihydro-lH-isoindolyi, 2,3-dihydro-lH-indolyl,
isoquinolinyl, quinolinyl, or naphthyl ring; and
(b) R2 and R2' are taken together with their
intervening atoms to form a substituted or unsubstituted
benzo, pyrido, pyrimido or partially unsaturated 6-
membered carbocyclo ring.
More preferred compounds of formula VIa have
one or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring

system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-e haloaliphatic group, a C1-6 aliphatic
group, phenyl, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4 - tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydxoquiholinyl, 2,3 -dihydro- Iff- isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or
naphthyl;
(b) R2 and R2' are taken together with their
intervening atoms to form a benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring
optionally substituted with -halo, -N(R4)2, -C1_4 alkyl,
-Ca-4 haloalkyl, -N02, -O(C1-4 alkyl) , -C02 (Ca-4 alkyl) , -CN,
-S02(C1.4 alkyl) , -SOsNHa, -0C(O)NH2, -NH2S02 (C1-4 alkyl) ,
-NHC(O) (C1-4 alkyl), -C(O)NH2/ and - CO (C1-4 alkyl), wherein
the (C1-4 alkyl) is a straight, branched, or cyclic alkyl
group; and
(c) Ring D is substituted by oxo or Rs, wherein
each Rs is independently selected from -halo, -CN, -N02,
-N(R4)2, optionally substituted C1-6 aliphatic group, -OR,
-C(O)R, -CO2R, -C0NH{R4), -N(R4)COR, -SO2N(R4)2, or
-N(R4)SO2R.
Even more preferred compounds of formula VIa
have one or more, and more preferably all, of the
features selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-4 aliphatic group optionally substituted
with halogen, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,

piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-t etrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, isoquinolinyl, quinolinyl, or
naphthyl;
(b) R2 and R2' are taken together with their
intervening atoms to form a benzo, pyrido, or partially
unsaturated 6-membered carbocyclo ring optionally
substituted with -halo, -N(R4)2, -C1-4 alkyl, -C1-4
haloalkyl, -N02, -0(d.4 alkyl) , -C02 (C1 alkyl) , -CN,
-SO2(C1-4 alkyl) , -SO2NH2, -OC(O)NH2/ -NH2SO2 (C1-4 alkyl) ,
-NHC(O) (C1-4 alkyl) , -C(O)NH2, or -C0(Ci.4 alkyl) , wherein
the (Ci_4 alkyl) is a straight, branched, or cyclic alkyl
group; and
(d) Ring D is substituted by oxo or Rs, wherein
each R5 is independently selected from -Cl, -F, -CN, -CF3,
-NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -o(C1-4
aliphatic), C1-4 aliphatic, and -CO2(C1.4 aliphatic).
Representative compounds of formula VI and XVa
are set forth in Table 5 below.

In another embodiment, this invention provides
a composition comprising a compound of formula VI or VIa
and a pharmaceutically acceptable carrier.
One aspect of this invention relates to a
method of inhibiting GSK-3 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula VI or VIa.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a GSK-3
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula VI or VIa.
Another aspect relates to a method of enhancing
glycogen synthesis and/or lowering blood levels of
glucose in a patient in need thereof, comprising

administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
VI or VIa. This method is especially useful for diabetic
patients.
Another aspect relates to a method of
inhibiting the production of hyperphosphorylated Tau
protein in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
VI or VIa. This method is especially useful in halting
or slowing the progression of Alzheimer's disease.
Another aspect relates to a method of
inhibiting the phosphorylation of p-catenin in a patient
in need thereof, comprising administering to said patient
a therapeutically effective amount of a composition
comprising a compound of formula VI or VIa. This method
is especially useful for treating schizophrenia.
One aspect of this invention relates to a
method of inhibiting Aurora activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula VI or VIa.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with an Aurora
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula VI or VIa. This method
is especially useful for treating cancer, such as colon,
ovarian, and breast cancer.
One aspect of this invention relates to a
method of inhibiting CDK-2 activity in a patient,
comprising administering to the patient a therapeutically

effective amount of a composition comprising a compound
of formula VI or VIa.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a CDK-2
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula VI or VIa. This method
is especially useful for treating cancer, Alzheimer's
disease, restenosis, angiogenesis, glomerulonephritis,
cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis,
alopecia, and autoimmune diseases such as rheumatoid
arthritis.
Another method relates to inhibiting GSK-3,
Aurora, or CDK-2 activity in a biological sample, which
method comprises contacting the biological sample with
the GSK-3 or Aurora inhibitor of formula VI or VIa, or a
pharmaceutical composition thereof, in an amount
effective to inhibit GSK-3, Aurora or CDK-2.
Each of the aforementioned methods directed, to
the inhibition of GSK-3, Aurora or CDK-2, or the
treatment of a disease alleviated thereby, is preferably
carried out with a preferred compound of formula VI or
VIa, as described above.
Another embodiment of this invention relates to
compounds of formula VII.

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
G is Ring C or Ring D;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-5 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8;
Ring D is a 5-7. membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or
heteroaryl ring, -Rs is hydrogen at each ortho carbon
position of Ring D;
R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R5, said C1-6 aliphatic group optionally

substituted with halo, cyano, nitro, or oxygen, or R1
and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
Ry is hydrogen or T-R3";
T is a valence bond, hydrogen, or a C1-4 alkylidene chain;
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4;
R3* is selected from an optionally substituted group
selected from C3-10 carbocyclyl, C6-10 aryl, a heteroaryl
ring having 5-10 ring atoms, or a heterocyclyl ring
having 5-10 ring atoms;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR,
-N(R4)2, -C0N(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)C0R,
-N(R4)CO2 (optionally substituted C1-6 aliphatic) ,
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-0R, -N(R4) CON(R4) 2,

-N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC(=O)N(R4)2, or R5 and
an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
V is -0-, -S-, -SO-, -S02-, -N(R6)SO2-, -SO2N(R6)-,
-N(R6)-, -CO-, -C02-, -N(R6)CO-, -N(R6) C(0) 0-,
-N(R6)CON(R6)-, -N(R6)SO2N(R6)-, -N(R6)N(R6) -,
-C(0)N(R6)-, -OC(O)N(R6)-, -C(RS)2O-, -C(Re)2S-,
-C(Re)2SO-, -C(R6)2SO2-, -C(R6)2S02N(R6)-, -C(R6) 2N(R6) -,
-C(R6)2N(R6)C(0)-, -C(R6)2N(R6)C(O)O-, -C(R6) =NN(R6)-,
-C(R6)=N-O-, -C(R6)2N(R6)N(R6)-, -C (R6) 2N (R6) SO2N (R6) - , or
-C (Rs) 2N (Re) CON (R6) - ;
W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-,
-C(R6)2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -C02-,
-C(RS)OC(O)-, -C(R6)0C(0)N(R6)-, -C (R6) 2N(RC) CO-,
-C(R6)2N(RS)C(O)O-, -C(R6)=NN(R6)-, -C(R6)=N-O-,
-C (R6) 2N (Re) N (R6) - , -C(R6) 2N (R6) S02N (R6) -,
-C(RS)2N(RG)CON(R6)-, or -CON(R6)-;
each R6 is independently selected from hydrogen, an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R8 is independently selected from an optionally
substituted C1-4 aliphatic group, -OR6, -SR6, -COR6,
-SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -C0N(R6)2, or
-CO2R6; and
R9 is selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR,
-N02, -CN, -S(0)R, -SO2R, -SR, -N(R4)2/ -CON(R4)2,

-SO2N(R4)2/ -OC(=0)R, -N(R4)COR, -N(R4) C02 (optionally
substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2,
-C=N-OR, -N(R4)CON(R4)2, -N(R4) SO2N(R4)2, -N(R4)SO2R, or
-OC(=O)N(R4)2.
Preferred Ry groups of formula VII include T-R3"
wherein T is a valence bond or a methylene. Preferred R3"
groups include an optionally substituted group selected
from C3-6 carbocyclyl, phenyl, or a 5-6 membered
heteroaryl or heterocyclyl ring. Examples of preferred Ry
include 2-pyridyl, 4-pyridyl, piperidinyl, cyclopropyl,
and an optionally substituted phenyl such as phenyl or
halo-substituted phenyl.
The R2 and R2' groups of formula VII may be
taken together to form a fused ring, thus providing a
bicyclic ring system containing a pyrazole ring.
Preferred fused rings include benzo, pyrido, pyrimido,
and a partially \msaturated 6-membered carbocyclo ring.
These are exemplified in the following formula VTI .
compounds having a pyrazole-containing bicyclic ring
system:

Preferred substituents on the R2/R2' fused ring
include one or more of the following: -halo, -N(R4)2, -C1-4
alkyl, -C1-4 naloalkyl, -NO2, -O (C1-4 alkyl) , -CO2(C1-4
alkyl), -CN, -SO2(C1-4 alkyl) , -SO2NH2, -OC(O)NH2,
-NH2SO2(C1-4 alkyl), -NHC(O) (C1-4 alkyl) , -C(O)NH2, and

-CO(C1-4 alkyl), wherein the (C1-4 alkyl) is a straight,
branched, or cyclic alkyl group. Preferably, the (C1-4
alkyl) group is methyl.
When the pyrazole ring system of formula VTI. is
monocyclic, preferred R2 groups include hydrogen, C1-4
aliphatic, alkoxycarbonyl, (un) substituted phenyl,
hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or
dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl,
dialkylaminoalkyl, phenylaminocarbonyl, and (N-
heterocyclyDcarbonyl. Examples of such preferred R2
substituents include methyl, cyclopropyl, ethyl,
isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H,
CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3,
CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CT2CH2NHCOOC (CH3) 3,
CONHCH(C3I3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, COKHCH2Ph,
CONH(cyclohexyl) , CON(Et)2, CON(CH3) CH2Ph, CONH(n-C3H7) ,
CON(Et)CH2CH2CH3, CONHCH2CH (CH3)2, CON(n-C3H7)2, CO(3-
methoxymethylpyrrolidin-1-yl), CONH(3-tolyl), CONH(4-
tolyl) , CONHCH3, CO(morpholin-l-yl) , CO(4-methylpiperazin-
1-yl) , CONHCH2CH2OH, CONH2/ and CO(piperidin-1-yl) . A
preferred R2' group is hydrogen.
When G is Ring C, preferred formula VTI Ring C
groups are phenyl and pyridinyl. When two adjacent
substituents on Ring C are taken together to form a fused
ring, Ring C is contained in a bicyclic ring system.
Preferred fused rings include a benzo or pyrido ring.
Such rings preferably are fused at ortho and meta
positions of Ring C. Examples of preferred bicyclic Ring
C systems include naphthyl and isoquinolinyl. Preferred
R1 groups include -halo, an optionally substituted Ca-6
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2/
-N(R6)2, -CO3R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2RS.
When R1 is an optionally substituted C1-6 aliphatic group,

the most preferred optional substituents are halogen.
Examples of preferred R1 groups include -CF3, -Cl, -F,
-CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2CH3, -CH3, -CF2CH3,
cyclohexyl, t-butyl, isopropyl, cyclopropyl, -CsCH,
-C=C-CH3, -SO2CH3, -SO2NH2, -N{CH3)2, -CO2CH3, -CONH2,
-NHCOCH3, -OC(O)NH2, -NHSO2CH3, and -OCF3..
On Ring C preferred R5 substituents, when
present, include -halo, -CN, -NO2, -N(R4)2, optionally
substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R,
-CONH(R4), -N(R4)COR, -SO2N(R4)2, and -N(R4) SO2R. More
preferred R5 substituents include -Cl, -F, -CN, -CF3,
-NH2, -HH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -O(C1-4
aliphatic), C1-4 aliphatic, and -CO2(C1-4 aliphatic).
Examples of such preferred R5 substituents include -Cl,
-F, -CN, -CF3, -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl,
cyclopropyl, isopropyl, t-butyl, and -CO2Et.
When G is Ring D, preferred formula VII Ring D
monocyclic rings include substituted and unsubstituted
phenyl, pyridinyl, piperidinyl, piperazinyl,
pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings.
When two adjacent substituents on Ring D are taken
together to form a fused ring, the Ring D system is
bicydic. Preferred formula VTI Ring D bicyclic rings
include 1,2,3,4-tetrahydroisoguinolinyl, 1,2,3,4-
tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, quinolinyl, and
naphthyl. Examples of more preferred bicyclic Ring D
systems include naphthyl and isoquinolinyl.
Preferred substituents on Ring D include one or
more of the following: halo, oxo, CN, -N02, -N(R4)2, -CO2R,
-CONH(R4), -N(R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR,
-C(O)R, or substituted or unsubstituted group selected
from 5-6 membered heterocyclyl, C6-10 aryl, or C1-6

aliphatic. More preferred Ring D substituents include
-halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a
substituted or unsubstituted group selected from 5-6
membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic.
Examples of Ring D substituents include -OH, phenyl,
methyl, CH2OH, CH2CH2OH, pyrrolidinyl, OPh, CF3, OCH, Cl,
Br, F, I, NH2, C(O)CH3, i-propyl, tert-butyl, SEt, OMe,
N(Me)2, methylene dioxy, and ethylene dioxy.
Preferred formula VII compounds have one or
more, and more preferably all, of the features selected
from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from a
naphthyl, quinolinyl or isoquinolinyl ring, and R1 is
-halo, an optionally substituted C1-6 aliphatic group,
phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -C0aR6,
-CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; or Ring D is an
optionally substituted ring selected from a phenyl,
pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl,
thienyl, azepanyl, morpholinyl, 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl,
2,3-dihydro- IH-isoindolyl, 2,3 -dihydro- 1H- indolyl,
isoquinolinyl, quinolinyl, or naphthyl ring;
(b) Ry is T-R3", wherein T is a valence bond or
a methylene; and
(c) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl,
heteroaryl, or a C1-6 aliphatic group, or R2 and R2' are
taken together with their intervening atoms to form a
substituted or unsubstituted benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring.
(b)
More preferred compounds of formula VII have
one or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic
group, phenyl, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-
dihydro-lH-indolyl, isoguinolinyl, quinolinyl, or
naphthyl;
(b) Ry is T-R3", wherein T is a valence bond or
a methylene and R3" is an optionally substituted group
selected from C3-6 carbocyclyl, phenyl, or a 5-6 membered
heteroaryl or heterocyclyl ring;
(c) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl, or
a C1-6 aliphatic group, or R2 and R2' are taken together
with their intervening atoms to form a substituted or
unsubstituted benzo, pyrido, pyrimido or partially
unsaturated 6-membered carbocyclo ring; and
(d) Ring D is substituted by oxo or R5, wherein
each R5 is independently selected from -halo, -CN, -N02,
-N{R4)a, optionally substituted C1-6 aliphatic group, -OR,
-C(O)R, -CO2R, -CONH(R4), -N(R4)COR, -SO2N(R4)2, or
-N(R4)SO2R.
Even more preferred compounds of formula VII
have one or more, and more preferably all, of the
features selected from the group consisting of:

(a) Ry is T-R3", wherein T is a valence bond or
a methylene and R3" is an optionally substituted group
selected from phenyl, or a 5-6 membered heteroaryl or
heterocyclyl ring;
(b) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-4 aliphatic group optionally substituted
with halogen, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisoguinolinyl, 1,2,3,4-
tetrahydroquinolinyl, isoguinolinyl, quinolinyl, or
naphthyl;
(c) R2 and R2' are taken together with their
intervening atoms to form a benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring
optionally substituted with -halo, -N(R4)2, -C1-4 alkyl,
-C1-4 haloalkyl, -N02, -O(C1-4 alkyl) , -CO2 (C1-4 alkyl) , -CN,
- S02 (C1-4 alkyl) , - SO2NH2, - OC (0) NH2, -NH2SO2 (C1-4 alkyl) ,
-NHC(O) (C1-4 alkyl) , -C(O)NH2, or -CO(C1-4 alkyl) , wherein
the (C1-4 alkyl) is a straight, branched, or cyclic alkyl
group; and
(d) Ring D is substituted by oxo or R5, wherein
each R5 is independently selected from -Cl, -F, -CN, -CF3,
-NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)2, -O(C1-4
aliphatic), C1-4 aliphatic, and -CO2(C1-4 aliphatic).
Representative compounds of formula VII are set
forth in Table 6 below.

In another embodiment, this invention provides
a composition comprising a compound of formula VTI and a
pharmaceutically acceptable carrier.

One aspect of this invention relates to a
method of inhibiting GSK-3 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula VII.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a GSK-3
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula VII.
Another aspect relates to a method of enhancing
glycogen synthesis and/or lowering blood levels of
glucose in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
VTI. This method is especially useful for diabetic
patients.
Another aspect relates to a method of
inhibiting the production of hyperphosphorylated Tau
protein in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
VII.' This method is especially useful in halting or
slowing the progression of Alzheimer's disease.
Another aspect relates to a method of
inhibiting the phosphorylation of ?-catenin in a patient
in need thereof, comprising administering to said patient
a therapeutically effective amount of a composition
comprising a compound of formula VTI. This method is
especially useful for treating schizophrenia.
One aspect of this invention relates to a
method of inhibiting Aurora activity in a patient,

comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula VT1.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with an Aurora
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula VII. This method is
especially useful for treating cancer, such as colon,
ovarian, and breast cancer.
One aspect of this invention relates to a
. method of inhibiting CDK-2 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula VII.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a CDK-2
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula VII. This method is
especially useful for treating cancer, Alzheimer's
disease, restenosis, angiogenesis, glomerulonephritis,
cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis,
alopecia, and autoimmune diseases such as rheumatoid
arthritis.
Another method relates to inhibiting GSK-3,
Aurora, or CDK-2 activity in a biological sample, which
method comprises contacting the biological sample with
the GSK-3 or Aurora inhibitor of formula VII, or a
pharmaceutical composition thereof, in an amount
effective to inhibit GSK-3, Aurora or CDK-2.

Each of the aforementioned methods directed to
the inhibition of GSK-3, Aurora or CDK-2, or the
treatment of a disease alleviated thereby, is preferably
carried out with a preferred compound of formula VII, as
described above.
Another embodiment of this invention relates to
compounds of formula VIII:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
Z1 is N or CR9, Z2 is N or CH, and Z3 is N or CRX, provided
that one of Z1 and Z3 is nitrogen;
G is Ring C or Ring D;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8;

Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
. substituted at any substitutable ring carbon by halo,
oxo, or -R5, and at any substitutable ring nitrogen by
-R4, provided that when Ring D is a six-membered aryl
or heteroaryl ring, -Rs is hydrogen at each ortho
carbon position of Ring D;
R1 is. selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -RB, said C1-6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or R1
and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
Rx is T-R3;
T is a valence bond or a C1-4 alkylidene chain;
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -NO2, -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -C0CH2C0R, -NO2, -CN, -S(O)R, -S(O)2R, -SR,
-N(R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR,

-N(R7)CO2 (optionally substituted C1-6 aliphatic),
-N(R4)N(R4)2, -C=NN(R4)2, -O=N-0R, -N(R7) CON(R7)2,
-N(R7)SO2N(R7)2, -N(R4)SO2R, or -OC(=O)N(R7)2;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted d1-6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,
-C(=O)R, -CO2R, -COCOR, -NO2, -CN, -S(O)R, -SOaR, -SR,
-N(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR,
-N(R4) CO2 (optionally substituted C1-6 aliphatic),
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N (R4) CON (R4) 2,
-N(R4)SO2N(R4)2l. -N(R4)SO2R, or -OC(=O)N(R4)2, or Rs and
an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
V is -O-, -S-, -SO-, -SOa-, -N(R*)SO2-, -S02N(RG)-,
-N(R6)-, -CO-, -COa-, -N(R6)CO-, -N(R6)C(O)O-,
-N(R6)CON(R6)-, • -N(R6)SO2N(R6)-, -N(R6)N(RS) - ,
-C(O)N(R6)-, -OC(O)N(R6)-, -C(Re)2O-, -C(R6)2S-,
-C(R6)2SO-, -C(R6)2SO2-, -C(RS)2SO2N(R6)-, -C (Rs) 2N (Rfi) - .
-C(R6)2N(R6)C(O)-, -C(R6)2N(R6)C(O)O-, -C (R6) =NN(R6) - ,
-C(RS)=N-O-, -C(R6)2N(R6)N(R6)-, -C (R6) 2N(R6) SO2N(Re) - , or
-C(R6)2N(R6)CON(R6)-;
W is -C(RS)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-,
-C(R6)2SO2N(Re)-, -C(R6)2N(R6)-, -CO-, -CO2-,
-C(R6)OC(O)-, -C(R6)OC(O)N(R6)-, -C (R6) 2N(R6) CO- ,
-C(R6)2N(RS)C(O)O-, -C(R€)=KN(R6)-, -C(RS)=N-O-,

-C(R6)2N(R6)N(R6)-, -C(R6)2N(R6)SO2N(R6)-,
-C(R6)2N(RS)CON(R6)-, or -CON(R6)-;
each R6 is independently selected from hydrogen, an
optionally substituted Ci.4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with' the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R8 is independently selected from an optionally
substituted Ca-4 aliphatic group, -OR6, -SR6, -COR6,
-SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -NO2, -CON(R6)2/ or
-CO2R6; and
R9 is selected from -R, halo, -OR, -C(=O)R, -CO2R, -COCOR,
-NOa, -CN, -S(O)R, -SO2R, -SR, -N(R*)2, -CON(R*)2,
-SO2N(R4)2, -OC(=O)R, -N(R4)C0R, -N(R4) CO2 (optionally
substituted Ca.6 aliphatic) , -N(R*)W(R*)2, -C=NN{R4)2,
-C=N-OR, -N(R*)CON(R4)2/ -N(R4) S02N(R4) 2, -N(R*)SO2R, or
-OC(=O)N(R4}2.
Accordingly, the present invention relates to
compounds of formula Villa, Vlllb, VTIIc and VHId as
sb.own below:

VIIIa VTIIb VIIIc VTIId
Preferred Rx groups of formula VIII include T-R3
wherein T is a valence bond or a methylene and R3 is CN,
-R, or -OR. When R3 is -R, preferred R3 groups include an
optionally substituted group selected from C1-6 aliphatic,
phenyl, or a 5-6 membered heteroaryl or heterocyclyl
ring. When R3 is -OR, preferred R groups include an
optionally substituted group C1-6 aliphatic group such as
alkyl- or dialkylaminoalkyl and aminoalkyl. Examples of
preferred Rx include acetamido, CN, piperidinyl,
piperazinyl, phenyl, pyridinyl, imidazol-1-yl, imidazol-
2-yl, cyclohexyl, cyclopropyl, methyl, ethyl, isopropyl,
t-butyl, NH2CH2CH2NH, and NH2CH2CH2O.
Preferred R9 groups of formula VIII, when
present, include R, OR, and N(R4)2. Examples of preferred
R9 include methyl, ethyl, NH2, NH2CH2CH2NH, N(CH3)2CH2CH2NH,
N{CH3)2CH2CH2O, (piperidin-l-yl)CH2CH2O, and NH2CH2CH2O.
The R2 and R2' groups of formula VIII may be
taken together to form a fused ring, thus providing a
bicyclic ring system containing a pyrazole ring.
Preferred fused rings include benzo, pyrido, pyrimido,
and a partially unsaturated 6-membered carbocyclo ring.
These are exemplified in the following formula VTII
compounds having a pyrazole-containing bicyclic ring
system:

Preferred substituents on the formula VIII
R2/R2' fused ring include one or more of the following:
-halo, -N(R4)a, -C1-4 alkyl, -d-4 haloalkyl, -NO2, -O(Cd-4
alkyl) , -CO2(C1-4, alkyl) , -CN, -S02 (C1-4 alkyl) , -SO2NH2,
-OC (O)NH2, -NH2SO2(C1-4 alkyl) , -NHC(O) (C1-4 alkyl) ,
-C(o)NH2. and -CO(C1-4 alkyl) , wherein the (C1-4 alkyl) is a
straight, branched, or cyclic alkyl group. Preferably,
the (d-4 alkyl) group is methyl.
When the pyrazole ring system of formula VIII
is monocyclic, preferred R2 groups include hydrogen, d-4
aliphatic, alkoxycarbonyl, (un) substituted phenyl,
hydxoxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or
dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl,
dialkylaminoalkyl, phenylaminocarbonyl, and (N-
heterocyclyl)carbonyl. Examples of such preferred R2
substituents include methyl, cyclopropyl, ethyl,
isopropyl, propyl, t-butyl, cyclopentyl, phenyl, C02H,
CO2CH3, CH2OH, CR2OCK3, CHfeCEfeCHzOH, CH2CH2CH2OCH3,
C3I2CH2CH2OC3J2Ph, CH2CH2CH2NH2 / CH2CH2CH2NHCOOC (CH3)3,
COKHCH(CH3)2, CONHCH2CH=CH2, CONHGH2CH2OCH3/ CONHCH2Ph,
CONH(cyclohexyl), CON(Et)2, CON(CH3) CH2Ph, CONH(n-C3H7) ,
CON(Et)CH2CH2CH3, CONHCH2CH (CH3) a, CON(n-C3H7) 2, C0(3-
methoxymethylpyrrolidin-1-yl), CONH(3-tolyl) , CONH(4-
tolyl) , CONHCH3, CO(morpholin-1-yl) , C0(4-methylpiperazin-
1-yl) , CONHCH2CH2OH, CONH2, and CO(piperidin-l-yl) . A
preferred R2' group is hydrogen.
When G is Ring C, preferred formula VIII Ring C
groups are phenyl and pyridinyl. When two adjacent
substituents on Ring C are taken together to form a fused
ring, Ring c is contained in a bicyclic ring system.
Preferred fused rings include a benzo or pyxido ring.
Such rings preferably are fused at ortho and meta

positions of Ring C. Examples of preferred bicyclic Ring
C systems include naphthyl and isoquinolinyl. Preferred
R1 groups include -halo, an optionally substituted C1-6
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2,
-N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6.
When R1 is an optionally substituted C1-6 aliphatic group,
the most preferred optional substituents are halogen.
Examples of preferred R1 groups include -CF3, -Cl, -F,
-CN, -COCH3, -OCH3, -OH, -CH2CH3, -OCH2CH3, -CH3, -CF2CH3,
cyclohexyl, t-butyl, isopropyl, cydopropyl, -OsCH,
-CsC-CH3/ -SO2CH3, -SOaNH2, -N(CH3)2, -CO2CH3, -CONH2,
-NHCOCH3, -OC(O)NH2f -NHSO2CH3, and -OCF3.
On Ring C preferred R5 substituents, when
present, include -halo, -CN, -N02, -N(R*)2/ optionally
substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R,
-C0NH(R4) , -N(R*)COR, -S02N(R4)2, and -N(R*)SO2R. More
preferred R5 substituents include -Cl, -F, -.CN, -CF3,
-NH2, -NH(Ci-4 aliphatic), -N(Ci_« aliphatic)2, -0(Ci-4
aliphatic), C^ aliphatic, and -CO2(d.4 aliphatic).
Examples of such preferred Rs substituents include -Cl,
-F, -CN, -CF3, -NH2, -NHMe, -NMe2, -OEt, methyl, ethyl,
cyclopropyl, isopropyl, t-butyl, and -CO2Et.
When G is Ring D, preferred formula VIII Ring D
monocyclic rings include substituted and unsubstituted
phenyl, pyridinyl, piperidinyl, piperazinyl,
pyrrolidinyl, thienyl, azepanyl, and morpholinyl rings.
When two adjacent substituents on Ring D are taken
together to form a fused ring, the Ring D system is
bicyclic. Preferred formula VTII Ring D bicyclic rings
include 1,2,3,4-tetrahydroisoquinplinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3-dihydro-1H- isoindolyl, 2,3-
dihydro-ltf-indolyl, isoquinolinyl, quinolinyl, and

naphthyl. Examples of more preferred bicyclic Ring D
systems include naphthyl and isoquinolinyl.
Preferred R5 eubstituents on Ring D of formula
VIII include halo, oxo, CN, -N02, -N{R4)2/ -CO2R,
-CONH(R4), -N(R4)COR, -SO2N(R4)2, -N(R4)SO2R, -SR, -OR,
-C(O)R, or substituted or unsubstituted group selected
from 5-6 membered heterocyclyl, C6-i0 aryl, or Ci-6
aliphatic. More preferred R* substituents include -halo,
-C3ST, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a substituted or
unsubstituted group selected from 5-6 membered
heterocyclyl, C6-io aryl, or C^g aliphatic. Examples of
Ring D substituents include -OH, phenyl, methyl, CH2OH,
CH2CH2OH, pyrrolidinyl, OPh, CF3, OsCH, Cl, Br, F, I, NH2,
C(O)CH3, i-propyl, Cert-butyl, SEt, OMe, N(Me)2, methylene
dioxy, and ethylene dioxy.
Preferred formula VIII compounds have one or
more, and more preferably all, of the features selected
from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from a
naphthyl, quinolinyl or isoquinolinyl ring, and R1 is
-halo, an optionally substituted Ci-e aliphatic group,
phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(Re)2, -CO2R6,
-C0NH2, -NHCORe, -OC(O)NH2, or -NHSO2R6; or Ring D is an
optionally substituted ring selected from a phenyl,
pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl,
thienyl, azepanyl, morpholinyl, 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroguinolinyl,
2,3-dihydro-lH-isoindolyl, 2,3-dihydro-lH-indolyl,
isoquinolinyl, quinolinyl, or naphthyl ring;

(b) Rx is T-R3 wherein T is a valence bond or a
methylene; and
(c) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl,
heteroaryl, or a C1-6 aliphatic group, or R2 and R2' are
taken together with their intervening atoms to form a
substituted or unsubstituted benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring.
More preferred compounds of formula VIII have
one or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic
group, phenyl, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4- tetrahydroisoguinolinyl, 1,2,3,4-
tetrahydxoquinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or
naphthyl; .
(b) Rx is T-R3 wherein T is a valence bond or a
methylene and R3 is CN, -R or -OR;
(c) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl, or
a C1-6 aliphatic group, or R2 and R2' are taken together
with their intervening atoms to form a substituted or
unsubstituted benzo, pyrido, pyrimido or partially
unsaturated 6-membered carbocyclo ring; and
(d) each R5 is independently selected from
-halo, -CN, -NO2, -N(R4)2, optionally substituted CC1-6
(b)
aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4) , -N(R4)COR,
-SO2N(R4)2, or -N(R4)SO2R.
Even more preferred compounds of formula VTII
have one or more, and more preferably all, of the
features selected from the group consisting of:
(a) Rx is T-R3 wherein T is a valence bond or a
methylene and R3 is -R or -OR wherein R is an optionally
substituted group selected from C1-6 aliphatic, phehyl, or
a 5-6 membered heteroaryl or heterocyclyl ring;
(b) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-4 aliphatic group optionally substituted
with halogen, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, isoquinolinyl, quinolinyl, or
naphthyl;
(c) R2 and R2' are taken together with their •
intervening atoms to form a benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring
optionally substituted with -halo, -N(R4)2, -C1-4 alkyl,
-C1-4 haloalkyl, -NO2, ~O(C1-4 alkyl), -CO2 (C1-4 alkyl) , -CN,
-SO2 (C1-4 alkyl) , -SO2NH2, -OC(O)NH2, -NH2SO2 (C1-4 alkyl) ,
-NHC(O) (C1-4 alkyl) , -C(O)NH2, or -CO (C1-4 alkyl) , wherein
the (C1-4 alkyl) is a straight, branched, or cyclic alkyl
group;
(d) each R5 is independently selected from -Cl,
-F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4
aliphatic)2, -0(C1-4 aliphatic) , C1-4 aliphatic, and
-CO2(C1-4 aliphatic) ; and
(c)

In another embodiment, this invention provides
a composition comprising a compound of formula VIII and a
pharmaceutically acceptable carrier.
One aspect of this invention relates to a
method of inhibiting GSK-3 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula VIII.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a GSK-3

inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula VIII.
Another aspect relates to a method of enhancing
glycogen synthesis and/or lowering blood levels of
glucose in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
VIII. This method is especially useful for diabetic
patients.
Another aspect relates to a method of
inhibiting the production of hyperphosphorylated Tau
protein in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
VIII. This method is especially useful in halting or
slowing the progression of Alzheimer's disease.
Another aspect relates to a method of
inhibiting the phosphorylation of ?-catenin in a patient
in need thereof, comprising administering to said patient
a therapeutically effective amount of a composition
comprising a compound of formula VIII. This method is
especially useful for treating schizophrenia.
One aspect of this invention relates to a
method of inhibiting Aurora activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula vIII.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with an Aurora
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a

therapeutically effective amount of a composition
comprising a compound of formula VIII. This method is
especially useful for treating cancer, such as colon,
ovarian, and breast cancer.
3 One aspect of this invention relates to a
method of inhibiting CDK-2 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula VIII.
) Another aspect relates to a method of treating
a disease that is alleviated by treatment with a CDK-2
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula VIII. This method is
especially useful for treating cancer, Alzheimer's
disease, restenosis, angiogenesis, glomerulonephritis,
cytomegalovirus, HIV, herpes, psoriasis, atherosclerosis,
alopecia, and autoimmune diseases such as rheumatoid
arthritis.
Another method relates to inhibiting GSK-3,
Aurora, or CDK-2 activity in a biological sample, which
method comprises contacting the biological sample with
the GSK-3 or Aurora inhibitor of formula VIII, or a
pharmaceutical composition thereof, in an amount
effective to inhibit GSK-3, Aurora or CDK-2.
Each of the aforementioned methods directed to
the inhibition of GSK-3, Aurora or CDK-2, or the
. treatment of a disease alleviated thereby, is preferably
) carried out with a preferred compound of formula VIII, as
described above.
The above formula I compounds contain a
pyrazole ring bearing the R2 and R2' substituents. In

their search for further inhibitors of the protein
kinases GSK and Aurora, applicants sought to replace the
pyrazole moiety of formula I with other heteroaromatic
rings. One of the more effective pyrazole ring
replacements was found to be a triazole ring. Inhibitors
having this triazole ring are otherwise structurally
similar to the formula I compounds and are represented by
the general formula IX:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
Z1 is nitrogen or OR9 and Z2 is nitrogen or CH, provided
that at least one of Z1 and Z2 is nitrogen;
G is Ring C or Ring D;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,

said fused ring being optionally substituted by halo,
oxo, or -R8;
Ring D is a 5-7 membered monocyclic ring or 8-10 tnembered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or
heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;
R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6
merabered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -RB, said C1-6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or R1
and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
merabered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
substituted by oxo or T-R3, and any substitutable
nitrogen on said ring formed by Rx and Ry is
substituted by R4;
T is a valence bond or a C1-4 alkylidene chain;
R2 is -R or -T-W-R6;

each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocydyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1-6 aliphatic) , -CON(R7):
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring,-
each R5 is independently selected from -R, halo, -OR,

each R6 is independently selected from hydrogen, an
optionally substituted C1-4 aliphatic gxoup, or two R6
groups on the same nitrogen atom are taken together -
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R8 is independently selected from an optionally

Compounds of formula IX may exist in
alternative tautomeric forms, as in tautomers 1-3 shown
below. Unless otherwise indicated, the representation of
any of these tautomers is meant to include the other two.

The Rx and Ry groups of formula IX may be taken
together to form a fused ring, providing a bicyclic ring
system containing Ring A. Preferred Rx/Ry rings include a
5-, 6-, 7-, or 8-membered unsaturated or partially
unsaturated ring having 0-2 heteroatoms, wherein said
Rx/Ry ring is optionally substituted. Examples of Ring A
systems are shown below by compounds IX-A through IX-DD,
wherein Z1 is nitrogen or C(R9) and Z2 is nitrogen or
C(H).

In the monocyclic Ring A system of formula IX,
preferred Rx groups include hydrogen, alkyl- or
dialkylamino, acetamido, or a C1-4 aliphatic group such as
methyl, ethyl, cyclopropyl, .isopropyl or t-butyl.
Preferred Ry groups, when present, include T-R3 wherein T
is a valence bond or a methylene, and R3 is -R, -N(R4)2,
or -OR. Examples of preferred RY include 2-pyridyl, 4-
pyridyl, piperidinyl, methyl, ethyl, cyclopropyl,
isopropyl, t-butyl, alkyl- or dialkylamino, acetamido,
optionally substituted phenyl such as phenyl or halo-
substituted phenyl, and methoxymethyl.

In the bicyclic Ring A system of formula IX,
the ring formed by Rx and Ry taken together may be
substituted or unsubstituted. Suitable substituents
include -R, halo, -OR, -C(=O)R, -CO2R, -COCOR, -N02, -CN,
-S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)2,
-OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted C1-6
aliphatic), -N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR,
-N(R4)CON(R4)2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or
-OC(=O)N(R4)2, wherein R and R4 are as defined above.
Preferred Rx/Ry ring substituents include -halo, -R, -OR,
-COR, -CO2R, -CON(R4)2, -CN, or -N(R4)2 wherein R is an
optionally substituted C1-6 aliphatic group.
Preferred R2 groups of formula IX include
hydrogen, C1-4 aliphatic, alkoxycarbonyl, (un) substituted
phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono-
or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl,
dialkylaminoalkyl, phenylaminocarbonyl, and (N-
heterocyclyl)carbonyl. Examples of such preferred R2
substituents include methyl, cyclopropyl, ethyl,
isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H,
CO2CH3, CH2OH, C3J2OCH3, CH2CH2CH2OH/ CH2CH2CH2OCH3,
CHzCHaCHaOCHaPh, CH2CH2CH2NH2, CH2CHaCH2NHCOOC(CH3) 3)
CONHCH(C3J3)2, CONHCH2CH=CH2, CONHCH2CH2OCH3, CONHCH2Ph,
CONH(cyclohexyl) , CON(Et)2, CON(CH3) CH2Ph, CONH(n-C3H7) ,
CON(Et)CH2CH2CH3, CONHCH2CH (CH3) 2, CON(n-C3H7) 2, C0(3-
methoxymethylpyrrolidin-1-yl) , CONH(3-tolyl) , C0NH(4-
tolyl) , CONHCH3, CO(morpholin-l-yl), C0(4-methylpiperazin-
1-yl) , CONHCH2CH2OH, CONH2, and CO (piperidin-1-yl) . A
more preferred R2 group for formula IX compounds is
hydrogen.
An embodiment that is particularly useful for
treating GSK3-mediated diseases relates to compounds of
formula X wherein, ring A is a pyrimidine ring:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridaziny1, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8;
R1 is selected from -halo, -CSS, -N02, T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R8, said C1-6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or R1
and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;

Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
substituted by oxo or T-R3, and any substitutable
nitrogen on said ring formed by Rx and Ry is
substituted by R4;

each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,

each R6 is independently selected from hydrogen, an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-S membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring; and
each R8 is independently selected from an optionally
substituted C1-4 aliphatic group, -OR6, -SR6, -COR6,
-SO3R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or
-CO2R6.
Compounds of formula X are structurally similar
to compounds of formula II except for the replacement of
the pyrazole ring moiety by the triazole ring moiety.

Preferred R2, Rx, Ry and Ring C groups of formula X are as
described above for the formula II compounds. Preferred
formula X compounds have one or more, and more preferably-
all, of the features selected from the group consisting
of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from a
naphthyl, quinolinyl or isoquinolinyl ring;
(b) Rx is hydrogen or C1-4 aliphatic and Ry is T-
R3, or Rx and Ry are taken together with their intervening
atoms to form an optionally substituted 5-7 membered
unsaturated or partially unsaturated ring having 0-2 ring
nitrogens ,-
(c) R1 is -halo, an optionally substituted C1-6
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2,
-N(R6)2, -CO2R6, -CONH2, -NHCOR6, -0C(0)NH2, or -NHSO2Re;
and
(d) R2 is hydrogen or a substituted or
unsubstituted group selected from aryl, heteroaryl, or a
C1-6 aliphatic group.
More preferred compounds of formula X have one
or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring;
(b) R* is hydrogen or methyl and Ry is -R,
N{R4)2, or -OR, or Rx and Ry are taken together with their
intervening atoms to form a benzo ring or a 5-7 membered
carbocyclo ring, wherein said ring formed by Rx and Ry is

(c) R1 is -halo, a C1-6 haloaliphatic group, a C1-6
aliphatic group, phenyl, or -CN;
(d) R2 is hydrogen or a substituted or
unsubstituted group selected from aryl or a C1-6 aliphatic
group; and
(e) each R5 is independently selected from
-halo, -CN, -N02, -N(R4)2, optionally substituted C1-6
aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR,
-SO2N(R4)2, or -N(R4)SO2R.
Even more preferred compounds of formula X have
one or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring;
(b)-Rx is hydrogen or methyl and Ry is methyl,
methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl,
alkyl- or an optionally substituted group selected from
2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry
are taken together with their intervening atoms to form
an optionally substituted benzo ring or a 6-membered
carbocyclo ring;
(c) R1 is -halo, a C1-4 aliphatic group
optionally substituted with halogen, or -CN;
(d) R2 is hydrogen or a C1-6 aliphatic group; and
(c)
(e) each R5 is independently selected from -Cl,
-F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4
aliphatic)2, -O(C1-4 aliphatic), C1-4 aliphatic, and
-C02 (C1-4 aliphatic) .
Another embodiment of this invention relates to
compounds of formula XI:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:.
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-R5, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or
heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;
Rx and Ry are taken together with their intervening atoms
to form a fused benzo ring or 5-8 membered carbocyclo
ring, wherein any substitutable carbon on said fused
ring formed by Rx and Ry is substituted by oxo or T-R3 ;
T is a valence bond or a C1-4 alkylidene chain;
R2 is -R or -T-W-R6;

each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,

each R6 is independently selected from hydrogen or an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring; and
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring.
Compounds of formula XI are structurally
similar to compounds of formula III except for the
replacement of the pyrazole ring moiety by the triazole
ring moiety. Preferred R2, Rx, Ry, and Ring D groups of
formula XI are as described above for the formula III
compounds. Preferred formula XI compounds have one or
more, and more preferably all, of the features selected
from the group consisting of:
(a) Ring D is an optionally substituted ring
selected from a phenyl, pyridinyl, piperidinyl,
piperazinyl, pyrrolidinyl, thienyl, azepanyl,
morpholinyl, 1,2,3,4-tetrahydroisoguinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or
naphthyl ring;
(b) Rx and Ry are taken together with their
intervening atoms to form an optionally substituted benzo
ring or 5-7 membered carbocyclo ring; and
(a)
(c) R2 is hydrogen or a substituted or
unsubstituted group selected from aryl, heteroaryl, or a
C1-6 aliphatic group.
More preferred compounds of formula XI have one
or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring D is an optionally substituted ring
selected from phenyl, pyridinyl, piperidinyl,
piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl,
2,3-dihydro- 1H-isoindolyl, 2,3 -dihydro-lH-indolyl,
isoquinolinyl, guinolinyl, or naphthyl;
(b) R* and Ry are taken together with their
intervening atoms to form a benzo ring or 5-7 membered
carbocyclo ring, wherein said ring formed by Rx and RY is
optionally substituted with -R, oxo, halo, -OR, -C(=O)R,
-CO2R, -COCOR, -NO2, -CN, -S(O)R, -SO2R, -SR, -N(R4)2,
-CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR,
-N(R4)CO2 (optionally substituted C1-6 aliphatic) ,
-N(R4)N{R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2,
-N(R4)S0aN(R4)2, -N(R4)SO2R, or -OC (=0)N (R4) 2;
(c) R2 is hydrogen or a substituted or
unsubstituted group selected from aryl or a C1-6 aliphatic
group; and
(d) each R5 is independently selected from halo,
oxo, CN, NO2, -N(R4)2, -CO2R, -CONH(R4) , -N(R4)COR,
-SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or a substituted
or unsubstituted group selected from 5-6 membered
heterocyclyl, C6-10 aryl, or C1-6 aliphatic.
Even more preferred compounds of formula XI
have one or more, and more preferably all, of the
features selected from the group consisting of:

(a) Rx and Ry axe taken together with their
intervening atoms to form a benzo ring or 6-membered
carbocyclo ring, wherein said ring formed by Rx and Ry is
optionally substituted with halo, CN, oxo, C1-6 alkyl, C1-6
alkoxy, (C1-6 alkyl) carbonyl, (C1-6 alkyl)sulfonyl, mono- or
dialkylamino, mono- or dialkylaminocarbonyl, mono- or
dialkylaminocarbonyloxy, or 5-6 membered heteroaryl;
(b) each R5 is independently selected from
-halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a
substituted or unsubstituted group selected from 5-6
membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic; and
(c) R2 is hydrogen or a C1-6 aliphatic group.
Another embodiment of this invention relates to
compounds of formula XII:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-Rs, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or

heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;
Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 1-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring is optionally and
independently substituted by T-R3, and any
substitutable nitrogen on said ring is substituted by
R4;

each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
each R4 is independently selected from -R7, -COR7,
-CO2 (optionally substituted C1-6 aliphatic) , -CON(R7)2,
or -SO2R7, or two R* on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR,

each R6 is independently selected from hydrogen or an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring; and
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl ring or
heteroaryl.
Compounds of formula XII are structurally
similar to compounds of formula IV except for the
replacement of the pyrazole ring moiety by the triazole
ring moiety. Preferred R2, Rx, Ry, and Ring D groups of
formula XII are as described above for the formula TV
compounds. Preferred formula XII compounds have one or

more, and more preferably all, of the features selected
from the group consisting of:
(a) Ring D is an optionally substituted ring
selected from a phenyl, pyridinyl, piperidinyl,
piperazinyl, pyrrolidinyl, thienyl, azepanyl,
morpholinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroguinolinyl, 2,3-dihydro-lH-isoindolyl, 2,3-
dihydro-lH-indolyl, isoquinolinyl, quinolinyl, or
naphthyl ring;
(b) Rx is hydrogen or C1-4 aliphatic and Ry is T-
R3, or Rx and Ry are taken together with their intervening
atoms to form an optionally substituted 5-7 membered
unsaturated or partially unsaturated ring having 1-2 ring
heteroatoms; and
(c) R2 is hydrogen or a substituted or
unsubstituted group selected from aryl, heteroaryl, or a
C1-6 aliphatic group.
More preferred compounds of formula XII have
one or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring D is an optionally substituted ring
selected from phenyl, pyridinyl, piperidinyl,
piperazinyl, pyrrolidinyl, morpholinyl, 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroguinolinyl,
2,3-dihydro-lH-isoindolyl, 2, 3-dihydro-lff-indolyl,
isoquinblinyl, quinolinyl, or naphthyl;
(b) R* is hydrogen or methyl and Ry is -R,
N(R*)2, or -OR, or Rx and Ry are taken together with their
intervening atoms to form a 5-7 membered unsaturated or
partially unsaturated ring having 1-2 ring nitrogens,
wherein said ring is optionally substituted with -R,
halo, oxo, -OR, -C(=O)R, -COaR, -COCOR, -NO2/ -CN, -S(O)R,
-S02R, -SR, -N(R*)2, -CON(R4)2, -SO2N(R4)2, -OC(=0)R,
(a)
-N(R4)COR, -N(R4)CO2 (optionally substituted C1-6 aliphatic) ,
-N(R4)N(R4)2, -C=NN(R4)2, -C=N-OR, -N(R4) CON(R4) 2,
-N(R4)SO2N(R4)2, -N(R4)SO2R, or -OC (=0)N(R4) 2;
(c) R2 is hydrogen or a substituted or
unsubstituted gxoup selected from aryl or a C1-6 aliphatic
group; and
(d) each R5 is independently selected from halo,
oxo, CN, NO2, -N(R4)2, -CO2R, -CONH(R4) , -N(R4)COR,
-SO2N(R4)2, -N(R4)SO2R, -SR, -OR, -C(O)R, or a substituted
or unsubstituted group selected from 5-6 metnbered
heterocyclyl, C6-10 aryl, or C1-6 aliphatic.
Even more preferred compounds of formula XII
have one or more, and more preferably all, of the
features selected from the group consisting of:
(a) Rx and Ry are taken together with their
intervening atoms to form a 6-membered unsaturated or
partially unsaturated ring having 1-2 ring nitrogens,
optionally substituted with halo, CN, oxo, C1-6 alkyl, C1-6
alkoxy, (C1-6 alkyl) carbonyl, (C1-6 alkyl) sulfonyl, mono- or
dialkylamino, mono- or dialkylaminocarbonyl, mono- or
dialkylaminocarbonyloxy,; or 5-6 membered heteroaryl;
(b) each R5 is independently selected from
-halo, -CN, -oxo, -SR, -OR, -N(R4)2, -C(O)R, or a
substituted or unsubstituted group selected from 5-6
membered heterocyclyl, C6-10 aryl, or C1-6 aliphatic; and
(c) R2 is hydrogen or a C1-6 aliphatic group.
Another embodiment of this invention relates to
compounds of formula XIII:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein:
Z1 is nitrogen, CRa, or CH, and Z2 is nitrogen or CH;
provided that one of Z1 and Z2 is nitrogen;
G is Ring C or Ring D;
Ring C is selected from' a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 metobered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8;
Ring D is a 5-7 membered monocyclic ring or 8-10 membered
bicyclic ring selected from aryl, heteroaryl,
heterocyclyl or carbocyclyl, said heteroaryl or
heterocyclyl ring having 1-4 ring heteroatoms selected
from nitrogen, oxygen or sulfur, wherein Ring D is
substituted at any substitutable ring carbon by oxo or
-Rs, and at any substitutable ring nitrogen by -R4,
provided that when Ring D is a six-membered aryl or.

heteroaryl ring, -R5 is hydrogen at each ortho carbon
position of Ring D;
R1 is selected from -halo, -CN, -N02, T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R8, said C1-6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or Rl
and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;

Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
substituted by oxo or T-R3, and any substitutable
nitrogen on said ring formed by Rx and Ry is
substituted by R4;
T is a valence bond or a C1-4 alkylidene chain;
R2 is -R or -T-W-R6;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -NO2, -CN, -S(O)R, -S(O)2R, -SR,
-N(R*)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR,
-N(R7) C02( optionally substituted Cj.-6 aliphatic),
-N(R*)N(R*)2, -C=NN(R4)2, -C=N-OR, -N (R7) CON (R7)2,
-N(R7)SO2N(R7)2, -N{R4)SO2R, or -OC(=O)N(R7)2;
each R is independently selected from hydrogen or an
optionally substituted group selected from Ci-e
aliphatic, C6_io aryl, a heteroaryl ring having 5-10
ring atoms, or a heterocyclyl ring having 5-10 ring
atoms;

each R6 is independently selected from hydrogen, an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;

each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7
on the same nitrogen are taken together with the
nitrogen to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R8 is independently selected from an optionally
substituted C1-4 aliphatic group, -OR6, -SR6, -COR6,-
-SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or
-CO2R6; and
Ra is selected from halo, -OR, -C(=O)R, -CO2R, -COCOR,
-N02/ -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2,
-SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) C02 (optionally
substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2,
-C=N-OR, -N(R4)CON(R4)2, -N{R4) SO2N(R4) 2, -N(R4)SO2R,
-OC(=O)N(R4)2, or an optionally substituted group
selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl
ring having 5-10 ring atoms, or a heterocyclyl ring
having 5-10 ring atoms.
Compounds of formula XIII may be represented by
specifying Z1 and Z2 as shown below:

Compounds of formula XIII are structurally
similar to compounds of formula V except for the
replacement of the pyrazole ring moiety by the triazole
ring moiety. Preferred R2, Rx, Ry, Ra, and Ring G groups

of formula XIII are as described above for the formula V
compounds. Preferred formula XIII compounds have one or
more, and more preferably all, of the .features selected
from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from a
naphthyl, quinolinyl or isoquinolinyl ring, and R1 is
-halo, an optionally substituted C1-6 aliphatic group,
phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2, -N(R6)2, -CO2R6,
-CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; or Ring D is an
optionally substituted ring selected from a phenyl,
pyridinyl, piperidinyl, piperazinyl, pyrrolidinyl,
thienyl, azepanyl, morpholinyl, 1,2,3,4-
tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinolinyl,
2,3 -dihydro- 1H-isoindolyl, 2,3 -dihydro- 1H-indolyl,
isoquinolinyl, quinolinyl, or naphthyl ring;
(b) Rx is hydrogen or C1-4 aliphatic and Ry is T-
R3, or Rx and Ry are taken together with their intervening
atoms to form an optionally substituted 5-7 membered
unsaturated. or partially unsaturated ring having 0-2 ring
nitrogens; and
(c) R2 is hydrogen or a substituted or
unsubstituted group selected from aryl, heteroaryl, or a
C1-6 aliphatic group.
More preferred compounds of formula XIII have
one or more, and more preferably all, of the features
selected from the group consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and

R1 is -halo, a C1-6 haloaliphatic group, a C1-6 aliphatic
group, phenyl, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, 2,3-dihydro-1H-isoindolyl, 2,3-
dihydro-lff-indolyl, isoquinolinyl, quinolinyl, or
naphthyl;
(b) Rx is hydrogen or methyl and Ry is -R,
N(R4)2, or -OR, or Rx and Ry are taken together with their
intervening atoms to form a benzo ring or a 5-7 membered
carbocyclo ring, wherein said ring formed by Rx and Ry is
optionally substituted with -R, halo, -OR, -C(=O)R, -CO2R,
-COCOR, -N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)a, -CON(R4)2,
-SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4) C02 (optionally
substituted C1-6 aliphatic) , -N(R4)N(R4)2, -C=NN(R4)2,
-C=N-OR, -N(R4)CON(R4)2/ -N(R4) SO2N(R4) 2, -N(R4)SO2R, or
-OC(=O)N(R4)2;
(c) R2 is hydrogen or a substituted or
unsubstituted group selected from aryl, or a C1-6
aliphatic group; and
(d) each Rs is independently selected from
-halo, -CN, -N02, -N(R4)2, optionally substituted C1-6
aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4) , -N(R4)COR,
-SO2N(R4)2, or -N(R4)SO2R, and, when Ring G is Ring D, Ring
D is substituted by oxo or R5.
Even more preferred compounds of formula XIII
have one or more, and more preferably all, of the
features selected from the group consisting of:
(a) R* is hydrogen or methyl and Ry is methyl,
methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl,
alkyl- or an optionally substituted group selected from
2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry

are taken together with their intervening atoms to form a
benzo ring or a 6-membered carbocyclo ring wherein said
ring formed by Rx and Ry is optionally substituted with
halo, CN, oxo, C1-6 alkyl, C1-6 alkoxy, (C1-6 alkyl) carbonyl,
(C1-6 alkyl) sulfonyl, mono- or dialkylamino, mono- or
dialkylaminocarbonyl, mono- or dialkylaminocarbonyloxy,
or 5-6 membered heteroaryl;
(b) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is a naphthyl ring, and
R1 is -halo, a C1-4 aliphatic group optionally substituted
with halogen, or -CN; or Ring D is an optionally
substituted ring selected from phenyl, pyridinyl,
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-
tetrahydroquinolinyl, isoquinolinyl, quinolinyl, or
naphthyl;
(c) R2 is hydrogen or a C1-6 aliphatic group; and
(d) each R5 is independently selected from -Cl,
-F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4
aliphatic)2/ -0(C1-4 aliphatic), C1-4 aliphatic, and
-CO2(C1-4 aliphatic) , and when Ring G is Ring D, Ring D is
substituted by oxo or R5.
Representative compounds of formula IX are
shown below in Table 8.

In another embodiment, this invention provides
a composition comprising a compound of formula IX and a
pharmaceutically acceptable carrier.
One aspect of this invention relates to a
method of inhibiting GSK-3 activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula IX.
Another aspect relates to a method of treating
a disease that is alleviated by treatment with a GSK-3
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula IX.
Another aspect relates to a method- of enhancing
glycogen synthesis and/or lowering blood levels of
glucose in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula
IX. This method is especially useful for diabetic
patients.
Another aspect relates to a method of
inhibiting the production of hyperphosphorylated Tau
protein in a patient in need thereof, comprising
administering to said patient a therapeutically effective
amount of a composition comprising a compound of formula

IX. This method is especially useful in halting or
slowing the progression of Alzheimer's disease.
Another aspect relates to a method of
inhibiting the phosphorylation of P-catenin in a patient
in need thereof, comprising administering to said patient
a therapeutically effective amount of a composition •
comprising a compound of formula IX. This method is
especially useful for treating schizophrenia.
One aspect of this invention relates to a
method of inhibiting Aurora activity in a patient,
comprising administering to the patient a therapeutically
effective amount of a composition comprising a compound
of formula IX. ' .
Another aspect relates to a method of treating
a disease that is alleviated by treatment with an Aurora
inhibitor, said method comprising the step of
administering to a patient in need of such a treatment a
therapeutically effective amount of a composition
comprising a compound of formula IX. This method is
especially, useful for treating cancer, such as colon,
ovarian, and breast cancer.
Another method relates to inhibiting GSK-3 or
Aurora activity in a biological sample, which method
comprises contacting the biological sample with the GSK-3
or Aurora inhibitor of formula IX, or a pharmaceutical
composition thereof, in an amount effective to inhibit
GSK-3 or Aurora.
Each of the aforementioned compositions and
methods directed to the inhibition of GSK-3 or Aurora, or
the treatment of a disease alleviated thereby, is
preferably carried out with a preferred compound of
formula IX, as described above.

The compounds of this invention may be prepared
as illustrated by the Synthetic Methods below, by the
Synthetic Examples described herein and by general
methods known to those skilled in the art.
General Synthetic Methods
The general synthetic methods below provide a
series of general reaction routes that were used to
prepare compounds of this invention. Methods A-F below
are particularly useful for preparing formula II
compounds. In most cases. Ring C is drawn as a phenyl
ring bearing an ortho R1 substituent. However, it will be
apparent to one skilled in the art that compounds having
other Ring C groups may be obtained in a similar manner.
Methods analogous to methods A-F are also useful for
preparing other compounds of this invention. Methods F-I
below are particulary useful for preparing compounds of
formula III or IV.

Method A is a general route for the preparation
of compounds wherein ring C is an aryl or heteroaryl
ring. Preparation of the starting dichloropyrimidine 1
may be achieved in a manner similar to that described in
Chem. Pharm. Bull., 30, 9, 1982, 3121-3124. The chlorine
in position 4 of intermediate 1 may be replaced by an
aminopyrazole or aminoindazole to provide intermediate 2

in a manner similar to that described in J. Med. Chem.,
38, 3547-3557 (1995). Ring C is then introduced using a
boronic ester under palladium catalysis (see Tetrahedron,
48, 37, 1992, 8II7-8126). This method is illustrated by
the following procedure.
A suspension of lff-quinazoline-2,4-dione (10.0
g, 61.7 mmol) in POCl3 (60 mL, 644 mmol) and N,N-
dimethylaniline (8mL, 63.1 mmol) is heated under reflux
for 2 h. Excess POCl3 is evaporated under vacuum, the
residue is poured into ice, and the precipitate is
collected by filtration. The crude solid 2,4-
dichloroquinazoline product may be used without further
purification.
To a solution of 2,4-dichloro-quinazoline (3.3
g, 16.6 mmol) in anhydrous ethanol (150 mL) is added 5-
methyl-lH-pyxazol-3-yl amine (3.2 g, 32.9 mmol). The
mixture is stirred at room temperature for 4 h, and the
resulting precipitate is collected by filtration, washed
with ethanol, and dried under vacuum to afford (2-chloro-
quinazolin-4-yl)-(5-methyl-lH-pyrazol-3-yl)-amine.
To a solution of (2-chloro-guinazolin-4-yl) - (5-
methyl-lH-pyrazol-3-yl)-amine (50 mg, 0.19 mmol) in DMF
(1.0 mL) is added the desired arylboronic acid (0.38
mmol), 2M Na2C03 (0.96 mmol), and tri-t-butylphosphine
(0.19 mmol). Under-nitrogen, PdCl2(dppf) (0.0II mmol) is
added in one portion. The reaction mixture is then
heated at 80°C for 5 to 10 hours, cooled to room
temperature, and poured into water (2 mL). The resulting
precipitate is collected by filtration, washed with
water, and purified by HPLC.

Methods B through F describe routes where the
pyrazole ring system is introduced after Ring C and the .
pyrimidine ring portion are first constructed. A
versatile intermediate is the 4-chloropyrimidine 4, which
is readily obtained from pyrimidinone 3 as shown in
Method B(i). This reaction sequence is generally
applicable for a variety of Ring C groups including
aliphatic, aryl, heteroaryl, or heterocyclyl. See J.
Med. Chem., 38, 3547-3557 (1995).
For quinazoline ring systems (where Rx and Ry
are taken together to form a benzo ring) , the useful
intermediate 6 may be obtained by condensing an
anthranilic acid or its derivative with a benzamidine as
shown in Method B(ii) or by condensing a benzoylchloride
with an anthranilamide as shown in Method B(iii) . Many
substituted anthranilic acid, anthranilamide, benzamidine
and benzoylchloride starting materials may be obtained by

known methods. See Aust. J. Chem., 38, 467-474 and J.
Med. Chem., 38, 3547-3557 (1995). Method B(iii) is
illustrated by the following procedure.
To a solution of anthranilamide (33 mmol) in
THF and CH2Cl2 (1:1, 70 mL) is added the desired
benzoylchloride (33 mmol) , and triethylamine (99 mmol) at
room temperature. The mixture is stirred for about 14
hours. The resulting precipitate is collected by
filtration, washed with CH2cl2 and water, and dried under
vacuum. The crude 2-behzoylaminobenzamide may be used
directly for the next step without further purification.
To a solution of the above crude product (13
mmol) in ethanol (50 mL) is added NaOEt (26 mmol) at room
temperature. The mixture is heated under reflux for 48
to 96 h. The solvent is evaporated and the "residue is
neutralized using concentrated HC1 to pH 7. The product
is then collected by filtration and dried under vacuum to
provide 2-phenyl-3H-guinazolin-4-one that may be used
without further purification.
To a suspension of the above product (12 mmol)
in POC13 (120 mmol) is added tri-n-propylamine (24 mmol) .
The mixture is heated under reflux for lh. After removal
of the excess POC13. by evaporation, the residue is
dissolved in ethyl acetate, and washed with IN NaOH
(twice) and water (twice). The organic layer is dried
over MgS04, the solvent is evaporated under vacuum, and
the crude product is purified by flash chromatography
(eluting with 10% of ethyl actetate in hexanes) to give
4-chloro-2-aryl guinazoline.
To a solution of 4-chloro-2-aryl guinazoline
(0.16 mmol) in DMF (or THF, ethanol) (1 mL) is added the
desired aminopyrazole or aminoindazole (0.32 mmol). The
mixture is heated in DMF (or THF under reflux) at 100 to

II0°C for 16 h (or in ethanol at 130-160°C for 16 hours)
and then poured into water (2 mL) . The precipitate is
collected by filtration and purified by HPLC.

Methods C and D(i) above employ p-ketoesters 8
and 10, respectively, as pyrimidinone precursors. The
substitution pattern of the Rx and Ry groups on the
pyrimidinone ring will be reversed if a chlorocrotonate
II (Synth. Comm, (1986), 997-1002), instead of the
corresponding P-ketoester 10, is condensed with the
desired benzamidine. These methods are illustrated by
the following general procedure.
To a solution of a p-ketoester (5.2' mmol) and
amidinium chloride (5.7 mtriol) in ethanol (5 mL) .is added
sodium ethoxide (7.8 mmol). The mixture is heated under
reflux for 7-14 hours. After evaporation the resulting
residue is dissolved in water, acidified with
concentrated HC1 to pH 6, and then filtered to obtain a
solid product 2-aryl-3H-pyrimidin-4-one (yield 75-87%) ,

which may be purified by flash column chromatography if
needed. To this pyrimidinone (3.7 mmol) is added POC13 (4
tnL) and n-Pr3N (1.4 mL) . The mixture is heated under
reflux for 1 hour. After evaporation of the excess POC13,
the residue is dissolved in ethyl acetate, washed with IN
NaOH solution (three times) and NaHCO3 (once) , and dried
over MgS04. The solvent is removed under vacuum and the
residue is purified by flash column chromatography
eluting with 10% of ethyl acetate in hexanes to give 2-
aryl-4-chloro-pyrimidine as a pale yellow syrup. This
crude product may be treated with a 3-aminopyrazole or 3-
aminoindazole as described above.

Method D(ii) above shows a general route for
the preparation of the present compounds, such as
compound 40, wherein Ry is N(R4)2. See II Farmaco, 52(1)
61-65 (1997) . Displacement of the S-chloro group is
exemplified here using morpholine. This method is
illustrated by the following procedure.
To a solution of 2-methylmalonic acid diethyl
ester (5 mmol) and sodium ethoxide (15 mmol) is added the

appropriate amidine salt (5 mmol) in ethanol (10 mL) and
the reaction heated at reflux for 2-24 hours. The
residue is dissolved in water and acidified with 2N HC1.
The resulting precipitate is filtered off and further
purified by flash chromatography (yield 5-35%) to afford
the pyrimidinedione 37. To 37 (1.6 mmol) is added POC13
(32 mmol) and tri-n-propylamine (6.4 mmol) and the
reaction refluxed is for lh. After evaporation of excess
POC13, the residue is dissolved in ethyl acetate, basified
with IN NaOH, separated and the aqueous phase twice more
extracted with ethyl acetate. The combined organics are
dried (sodium sulfate) and evaporated. Purification by
flash chromatography provides the dichloropyrimidine (38)
as a yellow oil in 23% yield.
A solution of 38 (0.33 mmol) in methanol (5 mL)
is treated with an amine, exemplified here using
morpholine (0.64 mmol) and refluxed 1 hour. After
evaporation of solvent, the residue is purified by flash
chromatography to provide the mono-chloropyrimidine 39 as
a colorless oil in 75% yield.
The mono-chloropyrimidine, 39, (0.19 mmol) may
be treated with a 3-aminopyrazole or 3-aminoindazole
compound in a manner substantially similar those
described above in Methods A and B.

(J. Org. Chem (1993), 58, 414-418; J.Med.Chem., (1992),
35, 1515-1520; J.Org.Chem., 91967, 32, 313-214). This
method is illustrated by the following general procedure.
The enamine is prepared according to w. White,
et al,J. Org Chem. (1967), 32, 213-214. The acyl
isocyanate is prepared according to G Bradley, et al, J
Med. Chem. (1992), 35, 1515-1520. The coupling reaction
then follows the procedure of S Kawamura, et al, J. Org.
Chem, (1993), 58, 414-418. To the enamine (10 mmol) in
tetrahydrofuran (30 mL) at 0°C under nitrogen is added
dropwise over 5 min a solution of acyl isocyanate (10
mmol) in tetrahydrofuran (5 tnL) . After stirring for 0.5
h> acetic acid (30 mL) is added, followed by ammonium
acetate (50 mmol). The mixture is refluxed for 2 h with
continuous removal of tetrahydrofuran. The reaction is
cooled to room temperature and is poured into water (100
mL) . The precipitate is filtered, washed with water and
ether and dried to provide the 2-aryl-3H-pyrimidin-4-one.

Method F shows a general route for the
preparation of the present compounds wherein Rx and Ry are
. taken together to form a 5-8 membered partially
unsaturated saturated or unsaturated ring having 1-3
heteroatoms. The condensation of a 2-amino-carboxylic
acid, such as 2-amino-nicotinic acid 13, and an acid
chloride 7 provides an oxazinone 14. Treatment of 14
. with ammonium hydroxide will furnish the benzamide 15

. which may be cyclized to a 2- (substituted) -pyrido [2,3-
d] [l,3]pyrimidin-4-one 16. This method is illustrated by
the following procedure.
2-(Trifluoromethyl)benzoyl chloride (4.2 ml,
29.2 mmol) is added dropwise to a solution of 2-
aminonicotinic acid (2.04g, 14.76 mmol) in 20 ml of
pyridine. The reaction mixture is. heated at 158 C for 30
min then cooled to room temperature. The reaction is
poured into 200 ml of water and an oil forms which
solidifies upon stirring. The solid is collected by
vacuum filtration and washed with water and diethyl
ether. The product is dried to give 2- (2-
trifluoromethyl-phenyl)-pyrido[2, 3-d] [1,3]oxazin-4-one
(2.56 g, 60% yield) which may be used in the next step
without further purification.
2- (2-Trif luoromethyl-phenyl) -pyrido [2,3-
d] [1,3] oxazin-4-one (2.51g) is stirred in 30% ammonium
hydroxide (25 ml) at room temperature overnight. The
resulting precipitate is filtered and rinsed with water
and diethyl ether. The precipitate is dried under vacuum
at 50 C overnight to give 2- (2-trifluoromethyl-
benzoylamino) -nicotinamide (850 mg, 33% yield)
2- (2-Trifluoromethyl-benzoylamino) -nicotinamide
(800mg, 2.6mmol) is dissolved in 10ml of ethanol.
Potassium ethoxide (435mg, 5.2mmol) is added to the
solution which is heated to reflux for 16 h. The
reaction mixture is evaporated in vacuo to afford a gummy
residue that is dissolved in water and acidified with 10%
sodium hydrogen sulfate to pH 7. The resulting
precipitate is filtered and dried under vacuum at 50 C to
give 2 - (2 -trifluoromethyl-phenyl) -3H-pyrido [2,3-
d] pyrimidin- 4 - one.

Method G
Method G is analogous to Method B(i) above.
This method is illustrated by the following general
procedure.
2- (3,4-Dichloro-phenyl) -3H-quinazolin-4-one
(lg, 3.43 mmol) is suspended in phosphorus oxychloride (4
mL) and the reaction mixture was stirred at II0°C for 3
hours. The solvents are then evaporated and the residue
is treated carefully with an ice cold aqueous saturated
solution of NaHCO3. The solid is collected by filtration
and washed with ether to give 4-chloro-2- (3,5-dichloro-
phenyl)-quinazoline as a white solid (993 mg, 93%).
To 4-chloro-2- (3,5-dichloro-phenyl) -quinazoline
(4.00mg, 1.29 mmol) in THF (30 mL) is added 3-amino-5-
methyl pyrazole (396 mg, 2.S8 mmol) and the reaction
mixture is heated at 65°C overnight. The solvents are
then evaporated and the residue triturated with ethyl
acetate, filtered and washed with a minimum amount of
ethanol to give [2- (3,4-dichlorophenyl) -quinazolin-4-yl] -
(5-methyl-2J?-pyrazol-3-yi)-amine as a white solid (3II mg
65%): mp 274°C; XH NMR (DMSO) 8 2.34 (3H, s) , 6.69 (1H,
s), 7.60 (1H, m), 7.84 (1H, d), 7.96 (2H, d), 8.39. (1H,
dd) , 8.60 (1H, d), 8.65 (1H, d), 10.51 (1H, s) , 12.30
(1H, S) ; IR (solid) 1619, 1600, 1559, 1528, 1476, 1449,
1376, 1352, 797, 764, 738; MS 370.5 (M+H)+.
The THF solvent used, in'the previous step may
be replaced by other organic solvents such as ethanol,
N,N-dimethylformamide, or dioxane.
Method H

Method H shows routes in which a Ring D aryl
group bearing a halogen (X is Br or I) may be converted
to other formula III compounds. Method H(i) shows a
phenylboronic acid coupling to Ring D to provide compound
18 and Method H(ii) shows an acetylene coupling to
provide compound 19. Substituent X in compound 17 may be
bromine or iodine. These methods are illustrated by the
following procedures.
Method H(i). To a mixture of [2-(4-bromo-
phenyl) -quinazolin-4-ylJ - (5-methyl-2H-pyrazol-3-yl) -amine
(196 mg, 0.51 mmol) and phenylboronic acid (75 mg, 0.62
mmol) in THF/water (l/l, 4 mL) is added Na2CO3 (219 mg,
2.06 mmol), triphenylphosphine (9mg, 1/15 mol%) and
palladium acetate (1 mg, 1/135 mol%). The mixture is
heated at 8 0°C overnight, the solvents are evaporated and
the residue is purified by flash chromatography (gradient
of CH2Clz/MeOH) to give (2-biphenyl-4-yl-quinazolin-4-yl) -
(5-methyI-21T-pyrazol-3-yl) -amine as a yellow solid (99
mg, SUli'-HHMR (DMSO) 8 2.37 (3H, s) , 6.82 (1H, s) , 7.39-

7.57 (4H, m), 7.73-7.87 (6H, m) , 8.57 (2H, d) , 8.67 (1H,
d), 10.42 {1H, s), 12.27 (1H, s); MS 378.2 (M+H)+
Method H(ii). To a mixture of [2-(4-bromo-
phenyl) -guinazolin-4-yl] - (5-methyl-2J-T-pyrazol-3-yl) -amine
(II4 mg, 0.3 imnol) , and trimethylsilylacetylene (147 mg,
1.5 mmoDin DMF (2 mL) is added Cul (1.1 mg, 1/50 mol%) ,
Pd(PPh3)2Cl2 (4.2 mg, 1/50 mol%) and triethylamine (121 mg,
0.36 mrnol) . The mixture is heated at 120°C overnight and
the solvent is evaporated. The residue is triturated in
ethyl acetate and the precipitate is collected by
filtration. ?
To the above precipitate suspended in THF (3
mL). is added tetrabutylammonium fluoride (1M in THF,
1.leq). The reaction mixture is stirred at room
temperature for two hours and the solvent is evaporated.
The- residue is purified by flash chromatography (gradient
of CH2Cl2/Me0H) to give [2- (4-ethynylphenyl) -quinazolin-4-
yl] - (5-tnethyl-2i?-pyrazol-3-yl)-amine as a white solid (68
mg, 70%): XH NMR (DMSO) 5 2.34 (3H, s)', 4.36 (1H, s) , 6.74
(1H, s), 7.55 (1H, m), 7.65 (2H, d) , 7.84 (2H, m), 8.47
(2H, d), 8.65 (1H, d), 10.43 (1H, s), 12.24 (1H, s); MS
326.1 (M+H)+

Method I above shows a general route for the
preparation of the present compounds wherein ring D is a
heteroaryl or heterocyclyl ring directly attached to the

pyrimidine 2-position via a nitrogen atom. Displacement
of the 2-chloro group, exemplified here using piperidine,
may be carried out in a manner similar to that described
in J. Med. Chem., 38, 2763-2773 (1995) and J. Chem. Soc.,
176-6-1771 (1948) . This method is illustrated by the
following procedure.
To a solution of (2-chloro-quinazolin-4-yl) -
(lfl"-indazol-3-yl)-amine (1 equivalent, 0.1-0.2 mmol) in
N, N-dimethylacetamide (1 ml) is added the desired amine
(3 equivalents) . ,The resulting mixture is maintained at
100°C for 6 h and then purified by reverse-phase HPLC.

Method J above shows the preparation of
compounds of formula V via the displacement of a chloro
group from an appropriately substituted pyridyl ring.
Method J(i) is a route for preparing compounds of formula
Va (see Indian J. Chem. Sect.B, 35, 8., 1996, 871-873) .
Method J(ii) is a route for preparing compounds of

formula Vb (see Bioorg. Med. Chem.,6, 12, 1998, 2449-
2458) . For convenience, the chloropyridines 21 and 23
are shown with a phenyl substituent corresponding to Ring
D of formula V. It would be apparent to one skilled in
the art that Method J is also useful for preparing
compounds of formula V wherein Ring D is heteroaryl,
heterocyclyl, carbocyclyl or other aryl rings. Method J
is illustrated by the following procedures.
Method J(i). (5-Methyl-2ff-pyrazol-3-yl) - (2-
phenyl-quinolin-4-yl) -amine. To 4-chloro-2-
phenylquinoline (J. Het. Chem., 20, 1983, 121-128)(0.53g,
2.21 mmol) in diphenylether (5 mL) was added 3-amino-5-
methylpyrazole (0.43g, 4.42 mmol) and the mixture was
heated at 200°C overnight with stirring. To the cooled
mixture was added petroleum ether (20 mL) and the
resulting crude precipitate was filtered and further
washed with petroleum ether. The crude solid was purified
by flash chromatography (SiO2, gradient DCM-MeOH) to give
the title compound as a white solid: mp 242-244°C; 1H NMR

phenyl - isoguinol in-1 -y 1) - amine. To 1 - chloro - 3 -
phenylisoquinoline (J. Het. Chem., 20, 1983, 121-
128)(0.33g, 1.37 mmol) in dry DMF (5 mL) was added 3-
amino-5-methylpyrazole (0.27g, 2.74 mmol) and potassium
carbonate (o.57g, 4.13 mmol)and the mixture was heated
under reflux for 6 hours. The mixture was cooled and the
bulk of DMF was evaporated. The residue was extracted
twice with ethyl acetate and the combined organic layers
were washed with brine, dried (MgSO4) , filtered and

concentrated. The crude was purified by flash - .
chromatography (SiO2, gradient DCM-MeOH) to give the title
compound as a colourless oil; 1H NMR (MeOD) ? 2.23 (3H,
s), 5.61 (1H, s), 7.41 (1H, m) , 7.52 (2H, m) , 7.62 (1H, tn) ,
7.81(1H, m), 8.07(lH, d) , 8.19(2H, m), 8.29(1H, s), 8.54
(1H, d); MS 301.2 (M+H)+

Method K shows a route for the preparation of
compounds of formula VI. A versatile starting material
is 2,4,6-trichloro-[1,3,5]triazine 25 in which the
chlorine substituents may be sequentially displaced. The
displacement of one of the chlorines by an aryl Grignard
reagent or an aryl boronic acid is described in PCT
patent application WO 01/25220 and Helv. Chim. Acta, 33,
1365 (1950). The displacement of one of the chlorines by
a heteroaryl' ring is described in WO 01/25220; J. Het.
Chem., II, 417 (1974); and Tetrahedron 31, 1879' (1975).
These reactions provide a 2,4-dichloro-(6-
substituted)[1,3,5]triazine 26 that is a useful
intermediate for the preparation of compounds of formula
VT. Alternatively, intermediate 26 may be obtained by
constructing the triazine ring by known methods. See US
patent 2,832,779; and US patent 2,691020 together with J.
Am. Chem. Soc. 60, 1656 (1938). In turn, one of the
chlorines of 26 may be displaced as described above to
provide 2-chloro-(4, 6-disubstituted) [1,3,5]triazine 27.

Method L shows a route for preparing compounds
of formula VTI. For illustration purposes the
trifluoromethylchalcone 28 is used as a starting
material; however, it would be apparent to one skilled in
the art that other rings may be used in place of the
trifluoromethylphenyl and phenyl rings of compound 28.
Substituted chalcones may be prepared by known methods,
for example as described in the Indian J. Chemistry, 32B,
449 (1993). Condensation of a chalcone with urea
provides the pyrimidinone 29, which may be treated with
POC13 to give the chloropyrimidine 30. See J. chem. Eng.
Data, 30(4) 512 (1985) and Egypt. J. Chem., 37(3), 283

(1994) . In an alternative approach to compound 30, one
of the aryl rings attached to the pyrimidine is
introduced by displacement of of the. 4-chloro group of
2,4-dichloro- (6-aryl) -pyrimidine by an aryl boronic acid
using a palladium catalyst such as (Ph3P)4Pd in the
presence of a base such as sodium carbonate as described
in Bioorg. Med. Lett., 9(7), 1057 (1999).- Displacement
of the chlorine of compound 30 by an appropriate
aminopyrazole provides compounds of this invention, such
as 31. The last step of this method is illustrated by
the following procedure.
[4- (4-Methylpiperidin-l-yl) -pyrimidin-2-yl] - (5-
methyl-2H-pyrazol-3-yl)-amine. To a solution of 2-
chloro-4 - (4-methylpiperidin-1 -yl) -pyrimidine (prepared
using a procedure similar to the one reported in Eur. J.
Med. Chem., 26(7) 729(1991)) (222 mg, 1.05 mmol) in BuOH
(5 mL) was added 3-amino-5-methyl-2H-pyrazole (305mg,
3.15 mmol) and the reaction mixture was then heated under
reflux overnight. The solvent was evaporated and the
residue dissolved in a mixture ethanol/water (1/3, 4 mL) .
Potassium carbonate (57mg, 0.41 mmol) was added and-the
mixture was stirred at room temperature for 2 hours. The
resulting suspension was filtered, washed with water
twice and rinsed with ether twice to give the title .
compound as a white solid (143mg, 50%): mp 193-195°C; XH
NMR (DMSO) 8 0.91 (3H, d) , 1.04 (2H, m) , 1.67 (3H, m) ,
2.16 (3H, s), 2.83 (2H, t), 4.31 (2H, m) , 6.19 (2H, m) ,
7.87 (1H, d), 8.80 (1H, br s), II.71 (1H, s); IR (solid)
1627, 1579, 1541, 1498, 1417, 1388, 1322-, 1246; MS
273.3(M+H)+.
Method M

Method M provides routes for obtaining
compounds of formula VTII. A general procedure far
displacing the chlorine of a 4-chloro-6-substituted-
pyridazine, 32, with an appropriately substituted
pyrazole to provide VTIIa is described in J. Het. Chem.,
20, 1473 (1983) . Analogous reactions may be carried out
as follows: (a) with 3-chloro-5-substituted-pyridazine,
33, to provide VTIIb is described in J. Wed. Chem.,
41(3), 3II (1998); (b) with 5-chloro-3-substituted-

[1,2,4] triazine, 34, to provide VTIIc is described in
Heterocydes, 26(12), 3259 (1987); and (c) with 3-chloro-
5-substituted- [1,2,4] triazine, 35, to provide VXIXd is
described in Pol. J. Chem., 57, 7, (1983); Xndian J".
Chem. Sect. B, 26, 496 (1987); and Agric. Biol. Chen?.,
54(12), 3367 (1990). An alternative procedure to
compounds of formula VTXlc is described in Indian J.
Chew. Sect. B, 29(5), 435 (1990).
Compounds of formula IX are prepared by methods
substantially similar to those described above for the
pyrazole-containing compounds of formula I. Methods A-J
may be used to prepare the triazole-containing compounds'
of formula IX by replacing the amino-pyrazole compound
with an amino-triazole compound. Such methods are
specifically exemplified by Synthetic Examples 415-422
set forth below. The amino-triazole intermediate may be
obtained by methods described in J. Org. Chem. USSR, 27,
952-957 (1991).
Certain synthetic intermediates that are useful
for preparing the protein kinase inhibitors of this
invention are. new. Accordingly, another aspect of this
invention relates to a 3-aminoindazole compound of
formula A:

where R10 is one to three substituents that are each
independently selected from fluoro, bromo, Ci-S haloalkyl,
nitro, or 1-pyrrolyl. Examples of such compounds include
the following:

wherein Rx and Ry are as defined above; R1 is selected
from Cl, F, CF3, CN, or NO2; and is one to three
substituents that are each independently selected from H,
Cl, F, CF3/ N02, or CN; provided that R1 and Rs are not
simultaneously Cl. Examples of compounds of formula B
are shown below:

In order that the invention described herein
may be more fully understood, the following examples • are
set forth. It should be understood that these examples
are for illustrative purposes only and are not to be
construed as limiting this invention in any manner.

SYNTHETIC EXAMPLE
The following HPLC methods were used in the
analysis of the compounds as specified in the Synthetic
Examples set forth below. As used herein, the term "Rt"
refers to the retention time observed for the compound
using the HPLC method specified.
HPLC-Method A:
Column: C18, 3 um, 2.1 X 50 mm, "Lighting" by Jones
Chromatography.
Gradient: 100% water (containing 1% acetonitrile,
0.1% TFA) to 100% acetonitrile (containing 0.1% TFA)
over.4.0 min, hold at 100% acetonitrile for 1.4 min
and return to initial conditions. Total run time 7.0
min. Flow rate: 0.8 mL/min.
HPLC-Method B:
Column: C18, 5 um, 4.6 X 150 mm "Dynamax" by Rainin
Gradient: 100% water (containing 1% acetonitrile,
0.1% TFA) to 100% acetonitrile (containing 0.1% TFA)
over 2 0 min,hold at 100% acetonitrile for 7.0 min
and return to initial conditions. Total run time
31.5 min. Flow rate: 1.0 mL/min.
HPLC-Method C:
Column: Cyano, 5 um, 4.6 X 150 mm "Microsorb" by
Varian.
Gradient: 99% water (0.1% TFA); 1% acetonitrile
(containing 0.1% TFA) to 50% water (0.1% TFA),' 50%
acetonitrile (containing 0.1% TFA) over 20 min, hold
for 8.0 min and return to initial conditions. Total
run time 30 min. Flow rate: 1.0 mL/min.

HPLC-Method D:
Column: Waters (YMC) ODS-AQ 2.0x50mm, S5, 120A.
Gradient: 90% water (0.2% Formic acid), 10%
acetonitrile (containing 0.1% Formic acid) to 10%
water (0.1% formic acid), 90% acetonitrile
(containing 0.1% formic acid) over 5.0 min, hold for
0.8 min and return to initial conditions. Total run
time 7. 0 min.
Flow rate: 1.0 mL/min.
HPLC-Method E:
Column: 50x2.0mm Hypersil C18 BDS;5 ?m
Gradient: elution 100% water (0.1% TFA), to 5% water
(0.1% TFA), 95% acetonitrile {containing 0.1% TFA)
over 2.1 min, returning to initial conditions after
2.3 min.
Flow rate; 1 mL/min.

Example 1 [2-(2-Clorophenyl)-5,6-dimethylpyrimidin.-4-yl]-
{5-Methyl-2H-pyrazol-3-yl)-amine (II-l) : ^-HNMR (500 MHz,
DMSO-d6) 610.4 (s, br, 1H) , 7.74 (m, 2H) , 7.68 (m, 1H) ,
7.60 (m, 1H), 6.39 (S, 1H), 2.52 (s, 3H), 2.30 (s, 3H),
2.22 (s, 3H);MS 314.1 (M+H).
Example 2 [2- (2-Chloro-phenyl)-6,1,8, 9-tetrahydro-5H-
cycloheptapyrimidin-4-yl3 - (lH-indazol-3-yl) -amine (II-2) :
Prepared in 30% yield. 1HNMR (500MHz, DMSO-d6) 5 1.72 (m,
4H), 1.91 (m, 2H), 3.02 (m, 4H), 7.05 (t, 1H), 7.33 (t,
1H), 7.39 (m, 1H), 7.47 (d, 1H), 7.55 (m, 3H), 7.59 (d,
1H), 10.4.(m, 1H) , 13.II (br. S, 1H) ; EI-MS 390.2 (M+H);
HPLC-Method A, Rt 2.99 min.

Example 3 (5-Fluoro-lH-indazol-3-yl)- [2-(2-
trifluoromethyl-phenyl) -5,6,7,8-tetrahydro-pyrido[3,4-
d]pyrimidin-4-yl]-amine (II-3) : Compound II-18 (90 mg,
0.17 mmol) was treated with an equal weight of Pd/C (10%)
in 4.4% formic acid in MeOH at room temperature for 14 h.
The mixture was filtered through celite, the filtrate was
evaporated, and crude product was purified by HPLC to
provide 18 mg (24%) of the desired product as pale yellow

Example 16 (5-Fluoro-lH-indazol-3-yl) - [2- (2-
trifluoromethyl-phenyl) -5,6,7,8-tetrahydro-pyrido [4,3-
dlpyrimidin-4-yl] -amine (II-16) -. A solution (of compound
II-12 (45mg, 0.087 mmol) in methanol (4.4% HCOOH) was
treated with an equal weight of Pd/C (10%) at room
temperature for 14 h. The mixture was filtered through
celite, the filtrate evaporated, and the crude product
was purified by preparative HPLC to provide 15 mg (41%)
of the desired product as yellow solid. 1HNMR (500 MHz,

Prepared in 58% yield. 1HNMR (500 MHz, DMSO-d6) 813.0
(s, 1H), 10.3 (s, br, 1H), 7.74 (m, 4H), 7.51 (d, 1H) ,
7.47 (d, 1H), 7.32 (t, 1H), 7.03 (t, 1H), 2.82 (m, 2H),
2.73 (lh, 2H), 1.90 (m, 4H) ppm; LC-MS (ES+) 410.21 (M+H);
HPLC-Method A, Rt 2.99 min.
Example 18 (7-Benzyl-2- (2 - trifluoromethyl-phenyl) -
5, 6,7, 8-tetrahydro-pyrido [4,3-d] pyrimidin-4-yl)-(5-
fluoro-U?-indazol-3-yl)-amine (II-18): Prepared from
compound Bll in 92% yield. 1HNMR (500 MHz, DMSO-d6)
812.9 {s, 1H) , 10.5 (s, br, 1H), 9.58 (s, 1H, TFA-OH),
7.71 (d, 1H), 7.52 (m, 9H), 7.19 (m, 2H), 4.57 (s, 2H) ,
4.20 (m, 2H) , 3.70 (m, 2H) , 3.00 (m, 2H) ppm; LC-MS (ES+)
519.23 (M+H); HPLC-Method A, Rt 3.23 min.
Example 19 (lff-Indazol-3-yl) - [6-methyl-2- (2-
trifluoromethyl-phenyl) -pyrimidin-4-yl] -amine (II-19) :
Prepared in 42% yield. Melting point 235-237°C; XHNMR
(500 MHz, DMSO) 8 2.44 (3H, s) , 7.09 (1H, J=7.5 Hz, t) ,
7.40 (1H, J=7.1 Hz, t), 7.49 (1H, J=8.3 Hz, d), 7.70 (3H,
m) , 7.79 (1H, J=7.3 Hz, t) , 7.87 (1H, J=8.3 Hz, d) , 8.03
(1H, J=7.7 Hz, d) , 10.3 (1H, s), 12.6 (1H, s) ppm; HPLC-
Method A, Rt 2.958 min; MS (P1A) 370.2 (M+H)+.
Example 20 (lH-Indazol-3-yl) - [6-phenyl-2- (2-
tr if luoromethyl-phenyl) -pyrimidin-4-yl] -amine (12-20) :
Prepared in 32% yield. ^HNMR (500 MHz, DMSO) 8 6.94 (1H,
J=7.4 Hz, t), 7.24 (1H, J=7.4 Hz, t) , 7.33 (1H, J=8.4 Hz,
d), 7.42 (3H, m), 7.57 (1H, J=7.3 Hz, t) , 7.68 (2S, tn) ,
7.75 (1H, J=7.9 Hz, d), 7.93 (3H, m), 8.18 (1H, br s),
10.45 (1H, br s) , 12.5 (1H, br s) ppm; HPLC-Method A, Rt
4.0 min; MS (FIA) 432.2 (M+H)+ .

Example 21 (lff-Indazol-3-yl) - [6- (pyridia-4-yl) -2- (2-
trifluoromethyl-phenyl)-pyrimidin-4-yl]-amine (II-21) :
Prepared in 12% yield. 1HNMR (500 MHz, DMSO) 5 7.16 (1H,
J=7.4 Hz, t), 7.46 (1H, J=7.6 Hz, t) , 7.55 (1H, J=8.3 Hz,
d) , 7.80 (1H, J=7.2 Hz, t), 7.90 (2H, m), 7.97 (1H, J=7.8
Hz, d) , 8.09 (1H, br) , 8.22 (2H, J=4.9 Hz, d) , 8.45 (1H,
br s), 8.93 (2H, J=4.8Hz, d) , 10.9 (1H, br s) , 12.8 (1H,
br s) ppmj HPLC-Method A, Rt 3.307 min; MS (FIA) 433.2
(M+H)+
Example 22 (lff-Xndazol-3-yl) - [6- (pyridin-2-yl) -2- (2-
trifluoromethyl-phenyl)-pyrimidin-4-yl]-amine (II-22):
Prepared in 42% yield. 1HNMR (500 MHz, DMSO) 8 7.07 (1H,
J=7.4 Hz, t), 7.36 (1H, J=7.4 Hz, t) , 7.46 (1H, J=7.4 Hz, .
d) , 7.53 (1H, J=5.0 Hz, t), 7.70 (1H, J=7.4 Hz, t), 7.79
(1H, J=7.1 Hz, t) , 7.83 (1H, J=7.4 Hz, d) , 7.88 (1H,
J=7.8 Hz, d), 7.97 (1H, J=7.7 Hz, t) , 8.02 (1H, J=5.5 Hz,
br d) , 8.36 (1H, J=7.8Hz, d) , 8.75 (2H, J=4.1Hz, d) ,
10.5 (1H, br s) , 12.7 (1H, br s) ppm; HPLC-Method A, Rt
3.677 min; MS (FIA) 433.2 (M+H) + .
Example 23 [6- (2-Chlorophenyl) -2- (2-trifluoromethyl-
phenyl) -pyrimidin-4-yl] - (lH-indazol-3-yl) -amine (II-23) :
Prepared in 44% yield; XHNMR (500 MHz, DMSO) S 7.08 (1H,
J=7.5 Hz, t) , 7.37 (1H, J=7.5 Hz, t) , 7.45 (1H, j=8.4 Hz,
d), 7.51 (2H, m), 7.61 (1H, J=7.4, 1.9 Hz, dd), 7.69 (2H,
m) , 7.79 (2H, J=4.0 Hz, d) , 7.86 (3H, J=7.8 Hz, d) , 8.04
(2H, J=6.2 Hz, br d) , 10.7 (1H, br s) , 12.6 (1H, br s)
ppm; HPLC-Method A, Rt 3.552 min; MS (FIA). 466.2 (M+H) + .
Example 24 [5,6 -Dimethyl - 2 - (2 - trif luoromethyl -phenyl) -
pyrimidin-4-yl] - (lH-indazol-3-yl)-amine (II-24) : Prepared
in 35% vield: mo 183-18C°C: XHNMR (500 MHz. DMSO) 5 2.14

(3H, s) , 2.27 (3H, s) , 6.85 (1H, J=7.5 Hz, t) , 7.15 (1H,
J=7.6 Hz, t), 7.32 (3H, m), 7.38 (1H, J=7.5 Hz, t), 7.42
(1H, J=7.4 Hz, t) , 7.53 (1H, J=7.6Hz, d) , 8.88 (1H, s) ,
12.5 (1H, s) ppm; HPLC-Method A, Rt 2.889 min. ; MS (FIA)
384.2 (M+H)'.
Example 25 [5, 6-Dimethyl-2- (2-trifluoroxnethyl-plaenyl) -
pyrimidin-4-ylJ - (5-fluoro-lff-indazol-3-yl) -amine (II-25) :
Prepared in 44% yield. Melting point 160-163°C; ^-HNMR
(500 MHz, DMSO) 5 2.27 (3H, s) , 2.40 (3H, s) , 7.16 (2H,
m) , 7.44 (2H, m), .7.52 (1H, J=7.4 Hz, t), 7.57 (1H, J=7.4
Hz, t) , 7.67 (1H, J=7.8 Hz, d) , 9.03 (1H, s) , 12.75 (1H,
s) ppm; HPLC-Method A, Rt 2.790 min,- MS (FIA) 402.2
(M+H)+.
Example 26 [2- (2-Chlorophenyl) -5, 6-dimethyl-pyrimidin-4-
yl]-(Iff-indazol-3-yl)-amine (II-26): Prepared in 30%
yield. 1HNMR (500 MHz, DMSO) 8 2.14 (3H, s) , 2.33 (3H,
s), 6.84 (1H, j=7.4 Hz, t), 7.13 (1H, J=7.4 Hz, t), 7.19
(1H, J=6.9 Hz, br t), 7.27 (1H, J=7.4 Hz, d) , 7.32 (3H,
brm), 7.37 (1H, J=7.1 Hz, d) , 10.0 (1H, br), 12.8 (1H,
br s) ppm; 8 2.919 min; MS (FIA) 350.1 (M+H)+.
Example 27 [5,6-Dimethyl-2- (2-trifluoromethyl-phenyl) -
pyrimidin-4-yl] - (7-f luoro-lff-indazol-3-yl) -amine (II-27) ::
Prepared in 92% yield. 1HNMR (500 MHz, DMSO) 8 2.33
(3H, s), 2.50 (3H, s)I 6.97 (1H, m), 7.15 (1H, m) , 7.30
(1H, J=8.1 Hz, d), 7.65 (3H, m), 7.76 (1H, J=7.5 Hz, d) ,
10.0 (1H, s) , 13.4 (1H, s) ppm; HPLC-Method A, Rt 3.053
min; MS (FIA) 402.2 (M+H) + .
Example 28 (5,7-Difluoro-lH-indazol-3-yl)-[5,6-Dimethyl-
2-(2-trifluoromethyl-phenyl) -pyrimidin-4-yl]-amine (II-

28).: Prepared in 50% yield. ^-HNMR (500 MHz, DMSO) 8 2.42
(3H, s) , 2.63 (3H, s) , 7.22 (1H, J=7.6 Hz, d) , 7.38 (1H,
J=9.3, 1.7 Hz, dt), 7.71 (1H, m) , 7.75 (1H, J=7.0 Hz, d) ,
7.79 (1H, J=6.7 Hz, d) , 7.86 (1H, J=8.0 Hz, d) , 10.0. (1H,
s) , 13.2 (1H, s) ppm; HPLC-Method-A, Rt 3.III min; MS
(FIA) 420.2 (M+H)+..
Example 29 [2- (2-Chlorophenyl) -5, 6-dimethyl-pyrimidin-4-
yl]-(5,7-difluoro-lH-indazol-3-yl)-amine (II-29):
Prepared in 58% yield. ^UNMR (500 MHz, DMSO) 8 2.47 (3H,
s), 2.66 (3H, s), 7.44 (2H, m) , 7.53 (1H, m) , 7.64 (3H,
m) , 10.4 (1H, br) , 13.8 (1H, br s) ppm; HPLC-Method A, Rt
2.921 min; MS (FIA) 386.1 (M+H)+.
Example 3 0 [2- (2-Chlorophenyl) -5, 6-dimethyl-pyrimidin-4-
yl] - (7-fluoro-lH-indazol-3-yl)-amine (II-30): Prepared in
70% yield. ^-HNMR (500 MHz, DMSO) 8 2.35 (3H", s) , 2.51
(3H, s) , 7.03 (1H, J=7.8, 4.4 Hz, dt) , 7-22 (1H, m) , 7.33
(1H, J=7.4 Hz, t) , 7.42 (1H, m) , 9.19 (1H, s) , 13.3 (1H,
s) ppm; HPLC-Method A, Rt 2.859 min; MS. (FIA) 368.2 .
(M+H) + .
Example 31 [2- (2-Chlorophenyl) -5, 6-dimethyl-pyrimidin-4-
yl] - (5-f luoro-lH-indazol-3-yl) -amine (II-31): Prepared in
86% yield. 1HNMR (500 MHz, DMSO) 8 2.49 (3H, s), 2.68
(3H, s) , 7.38 (1H, J=9.0 Hz, t) , 7.54 (2H, m) , 7.67 (4H,
m) , 10.5 (1H, br), 13.2 (1H, br s) ppm; HPLC-Method A, Rt
2.850 min; MS (FIA) 368.1 (M+H) + .
Example 32 [2-(2,4-Dichlorophenyl)-5, e-dimethyl-
pyrimidin^-yl] - (lff-indazol-3-yl)-amine (II-32): Prepared
in 52% yield. 1HNMR (500 MHz, DMSO) 5 2.46 (3H, s) , 2.64

(3H, s) , 7.16 (1H, J=7.5 Hz, t) , 7.46 (1H, J=7.6 Hz, t) ,
7.61 (2H, m) , 7.68 (2H, J=8.2 Hz, d) , 7.82 (1H, m) , 10.2
(1H, br) , 13.0 (1H, br s) ppm; HPLC-Method A, Rt 2.983.
min; MS (FIA) 384.1 (M+H).
Example 33 (5-Methyl-2ff-pyrazol-3-yl) - [2- (2-
methylpnenyl)-quinazolin-4-yl]-amine (II-33): 1HNMR (DMSO)
5 1.21 (3H,s), 2.25 (3H, s) , 6.53 (1H, s), 7.38 (4H, m) ,
7.62 (1H, d) , 7.73 (1-H, d) , 7.81 (1H, d) , 7.89 (1H, t) ,
8.70 (1H, s), 12.20 (1H, s) ; MS 316.3 (M+H)+.
Example 34 [2- (2,4-Dif luorophenyl) -quinazolin-4-yl] - (5-
methyl-2ff-pyrazol-3-yl)-amine (II-34): 1HNMR (500 MHz,
DMSO-d6) 812.4 (br s, 1H) , 10.8 (br s, 1H) , 8.58 (d, 1H) ,
7.97 {m, 1H) , 8.36 (m, 1H) , 7.85 (m, 1H) , 7.60 (m, 1H) ,
6.62 (s, 1H) , 2.30 (s, 3H) ; MS 338.07 (M+H).
Example 35 [2- (2,5-Dimethoxypb.enyl) -quinazolin-4-yl] - (5-
methyl-2H-pyrazol-3-yl)-amine (II-35): 1HNMR (500 MHz,
DMSO-d6) 812.5 (br s, 1H) , 8.68 (br, 1H) , 7.92 (t, J =
7.5 Hz, 1H), 7.86 (d, J = 8.2. Hz, 1H) , 7.65 (t, J = 7.5
Hz, 1H), 7.45 (s, 1H) , 7.14 (m, 2H), 6.51 (s, 1H), 3.79
(s, 3H), 3.67 (s, 3H), 2.14 (s, 3H); MS 362.2 (M+H).
Example 36 [2- (2-Chlorophenyl) -quinazolin-4-yl] - (5-
methyl-2H-pyrazol-3-yl)-amine (II-36): 1HNMR (500 MHz,
DMSO-d6) 8II.8 (br, 1H) , 8.80 (d, J =8.3 Hz, 1H) , 8-00
(t, J = 7.6 Hz, 1H), 7.82 (d, J = 8.3 Hz, 1H) , 7.78 (m,
2H), 7.67 (d, J = 7.8 Hz, 1H) , 7.61 (t, J = 7.0 Hz, 1H) ,
7.55 (t, J = 7.4 Hz, 1H) , 6.56 (s, 1H), 2.18 (s, 3H); MS
336.1 (M+H).

Example 37 [2- (2-Metnoxyphenyl) -quinazolin-4-yl] - (5-
methyl-2H-pyrazol-3-yl)-amine (II-37): 1HNMR (500 MHz,
DMSO-d6) 5 8.78 (s, br, 1H) , 8.00 (t, J = 7.4 Hz, 1H) ,
7.90 (m, 2H) , 7.74 (t, J = 7.5 Hz, 1H) , 7.63 (t, J = 7.3
HZ, 1H), 7.30 (d, J = 8.4 Hz, 1H) , 7.18 (t, J = 7.5 Hz,
1H) , 6.58 (s, br, 1H) , 3.90 (s. 3H) , 2.21 (s, 3H) ; MS
332.1 (M+H).
Example 38 [2- (2,6-Dimethylphenyl) -quinazolin-4-yl] - (5-
methyl-2H-pyrazol-3-yl)-amine (II-38): 1HNMR (500 MHz,
DMSO-d6) 512.2 (s, br, 2H) , 8.88 (d, J ? 7.7 Hz, 1H) ,
8.05 (t, J = 7.7 Hz, 1H), 7.80 (m, 2H) , 7.37 (t, J = 7.6
Hz, 1H) , 7.21 (d, J = 7.7 Hz, 2H), 6.36 (s, 1H) , 2.16 (s,
3H), 2.15 (s, 6H); MS 330.1 (M+H).
Example 39 [2- (2-Acetylpb.enyl) -quinazolin-4-yl] - (5-
metnyl-2H-pyrazol-3-yl)-amine (II-39): 1HNMR (500 MHz,
DMSO-d6) 512.35 (s, br, 1H) , 8.93 (d, J = 8.4 Hz, 1H) ,
8.37 (d, J = 8.6 Hz, 1H), 8.20 (d, J = 7.6 Hz, 1H), 8.II
(t, J = 8.0 Hz, 2H) , 7.89 (m, 2H) , 7.77 (m, 2H) , 6.93 (s,
1H) , 2.33 (s, 3H) , 2.04 (s, 3H). MS 344.1 (M+H).
Example 40' [2- (2,3-Dimethylphenyl) -quinazolin-4-yl] - (5-
meth.yl-r2H-pyrazol-3-yl)-amine (II-40): 1HNMR (500 MHz,
DMSO-d6) 512.6 (s, br, 1H) , 12.1 (s, br, iH) , 8.91 (d, J
- 7.7 Hz, IH), 8.14 (t, J = 7.2 Hz, IH), 7.95 (d, J = 8.4
Hz, IH), 7.89 (t, J = 7.7 Hz, IH), 7.58 (d, J = 7.6 Hz,
IH) , 7.53 (d, J = 7.0 Hz,' IH) , 7.42 (t, J = 7.6 Hz, IH) ,
6.60 (s, IH), 2.43 (s, 3H), 2.35 (s, 3H), 2.32 (s, 3H) ;
MS 330.1 (M+H).
Examp]a 41 (5-Methyl-2ff-pyrazol-3-yl) - [2- (2-
trifluoromethylphenyl) -quinazolin-4-yl] -amine (II-41) :

1HNMR (500 MHz, DMSO-d6) 812.3 {s, 1H) , 10.5 (s, 1H) ,
8.77 (d, J = 8.2 Hz, 1H), 7.92 (m, 2H) , 7.85 (in, 3H) ,
7.56 (t, J = 8.1 Hz, 1H), 7.67 (t, J = 7.4 Hz, 1H), 6.63
(s, 1H), 2.27 (s, 3H); MS 370.1 (M+H).
Example 42 [2- (2-Ethylphenyl) -quinazolin-4-yl] - (5-Methyl-
2H-pyrazol-3-yl) -amine (II-42): 1HNMR (500 MHz, DMSO-d6)
88.80 (tn, 1H) , 8.02 (s, br, 1H) , 7.82' (d, J = 8.4 Hz,
1H) , 7.77 (m, 1H) , 7.62 (d, J = 7.6 Hz, 1H) , 7.54 (m,
1H), 7.41 (m, 2H), 6.40 (s, 1H) , 2.75 (g, J = 7.1 Hz,
2H), 2.17 (s, 3H), 0.99 (t, J = 7.5 Hz, 3H) ; MS 330.1
(M+H) .
Example 43 (2-Biphenyl-2-yl-quinazolin-4-yl) - (5-methyl-
2H-pyrazol-3-yl)-amine (II-43): 1HNMR (500 MHz, DMSO-d6)
8 8.76 (d, J = 7.6 Hz", 1H) , 8.04 (m, 1H) , 7.75 (m, 6H) .
7.30 (m, 5H), 5.34 (s, 1H), 2.14 (s, 3H); MS 378.2 (M+H).
Example 44 12- (2-Hydroxyphenyl) -quinazolin-4-yl] - (5-
Methyl-2B'-pyrazol-3-yl)-amine (II-44): 1HNMR (500 MHz,
DMSO-d6) 810.9 (s, br, 1H) , 8.62 (d, J = 8.2 Hz, 1H) ,
8.28 (d, J = 7.9 Hz, 1H) , 7.87 (m, 2H), 7.60 (t, J = 7.9
Hz, 1H) , 7.37 (t, J = 7.8 Hz, 1H) , 6.92 (m, 2H) , 6.45 (is,
1H), 2.27 (s, 3H); MS 318.1 (M+H).
Example 45 [2-(2-Etnoxyplienyl)-quinazolin-4-yl] - (5-
Methyl-2H-pyrazol-3-yl.) -amine (II-45) : ^HNMR (500 MHz,
DMSO-d6) 812.1 (s, br, 1H)-, 8.75 (d, J = 8.3 Hz, 1H) ,
7.97 (t, J = 7.8 Hz, 1H) , 7.82 (d, J = 8.3 Hz, 1H), 7.78
(d, J = 7.5 Hz, 1H) , 7.70 (t, J = 7.8 Hz, .'lH) , 7.56 (t, J
= 7.8 Hz, 1H), 7.22 (d, J = 8.4 lHz, 1H) , 7.12 (t, J = 7.6
Hz, 1H), 6.55 (s, 1H), 4.II (q, J = 6.9 Hz, 2H), 2.16 (s,
3H), 1.22 (t, J = 6.9 Hz, 3H) ; MS 346.1 (M+H).

Example 46 [5- (Thiophen-2-yl) -2#-pyrazol-3-yl] - [2- (2-
trifluoroaethylphenyl) -quinazolin.-4-yi] -amine (II-46) :
1HNMR.(500 MHz, DMSO-d6) 5 8.04 (d, J = 8.3 Hz, 1H) , 8.05
(dd, J = 7.3, 8.2 Hz, 1H), 7.93 (d, J = S.5 Hz, 1H), 7.81
(m, 5H) , 7.34 (d, J = 5.0 Hz, 1H), 7.25 (m, 1H), 7.00 (m,
1H), 6.87 (s, 1H); MS 438.1 (M+H).
Example 47 [4-(Thiophen-2-yl)-Zff-pyrazol-3-yl] -[2-(2-
trifluoromethylphenyl) -quinazolin-4-yl] -amine (II-47) :
Prepared according to Method B. XHNMR (500MHz, DMSO-d6) 5
6.97 (m, 1H), 7.08 (m, 1H), 7.27 (m, 1H), 7.36 (m, 1H) ,
7.66 (m, 2H), 7.77 (m, 3H), 7.83 (m, 1H), 8.00 (m, 1H),
8.18 (s, 1H) , 8.62 (d, J =8.2 Hz, 1H) , 10.7 {br. S, 1H);
EI-MS 438.1 (M+H); HPLC-Method A, Rt 2.97 min.
Example 48 (4-Phenyl-2ff-pyrazol-3-yl)-[2-(2-
trifluorometb.ylpben.yl) -quinazolin-4-yl] -amine (21-48) :
Prepared according to Method B. 1HNMR (500MHz, DMSO-d6) 5
7.05 (br. s, 1H), 7.14 (t, J = 7.8 Hz, 1H), 7.25 (m, 3H),
7.43 (m, 2H) , 7.60 (m, 2H) , 7.73 (m, 2H) , 7.80 (d, 1H) ,
7.95 (m, 1H), 8.12 (br. s, 1H), 8.60 (m, 1H) , 10.6 (br.
S, 1H) ; EI-MS 432.2 (M+H); HPLC-Method A, Rt 3.04 min.
Example 49 (5-tejrt-Butyl-2H-pyrazol-3-yl) - [2- (2-
trifluoromethyl-phenyl) -guinazolin-4-yl] -amine (II-49) :
1HNMR (500 MHz, DMS0-d6) 8 8.76 (d, J = 8.3 Hz, 1H), 7.94
(m, 2H), 7.75 (m, 4H), 7.70 (t, J = 7.6 Hz, 1H), 6.51 (s,
1H) , 1.16 (s, 9H); MS 412.2 (M+H).
Example 50 (5-Pbenyl-2H-pyrazol-3-yl)-[2-(2-
trif luoromethylphenyl) - quinazolin- 4 -yl ] - amine (II-50) :
^•HNMR (500MHz, DMSO-d6) 8 7.09 (s, 1H) , 7.36 (td, J = 7.8,

1.1 Hz, 1H) , 7.46 (t, J = 7.8 Hz, 2H) , 7.65 (br. d, J «
8.1 Hz, 2H) , 7.78 (m, 2H) , 7.90 (tn, 4H) , 7.95 (d, J - 7.7
Hz, 1H) , 8.00 (t, J B 7.8 Hz, 1H) , 8.81 (d, J = 8.6 Hz,
1H) , II.29 (br. s, 1H) ; El-MS 432.1 (M+H) ; HPLC-Method A,
Rt 3.24 min.
Example 51 (4,5-Diphenyl-2ff-pyrazol-3-yl) - [2- (2-
trlf luoromethylphcnyl) -guinazolln-4-yl] -amine (II-51) :
1HNMR (500MHz, DMS0-d6) 6 7.13 (m, 1H) , 7.18 (m, 5H) , 7.36
(m, 5H), 7.62 (m, 3H) , 7.73 (m, 2H) , 7.85 (m, 1H), 8.48
(d, J = 8.7 Hz, 1H) , 10.02 (s, 1H) , 13.19 (s, 1H) ; EI-MS
5t)8.2 (M+H); HPLC-Metnod A, Rt 3.39 min.
Example 52 (4-Carbaiaoyl-2S-pyrazol-3-yl) - [2-(2-
trifluorometh.ylph.enyl) -quinazolin-4-yl] -amlne (II-52) :
Prepared in 40% yield. 1HNMR (500MHz, DMS0-d6) : 5 12.85
(s, 1H) , 12.77 (s, 1H) , II.80 (s, 1H) , 10.80 (s, 1H) ,
8.35-7.42 (m, 9H) ; MS 399.13 (M+H) HPLC-Method'A, Rt
2.782 min.
Example 53 (2J?-Pyrazol-3-yl) - 12- (2-
trifluoromethylphenyl) -quinazolin-4-yl] -amine (II-53) :
Prepared in 38% yield. 1HNMR (500 MHz, DMSO-d6) 8 12.52
(s, 1H), 10.65 (s, 1H), 8.75 (d,.1H) , 7.91-7.68 (m, BH),
6.87 (s, 1H) . MS: (M+H) 356.17. HPLC-Method A, Rt 2.798
min.
Example 54 (5-Hydroxy-2H-pyrazol-3-yl) - [2- (2-
trifliioromethylphenyl) -quinazolln-4-yl] -amine (II-54) :
Prepared in 36% yield; 1HNMR (500 MHz, DMSO-d6) 5 10.61
(6, 1H), 8.75 (s, 1H), 8.03-7.75 (m, 9H), 5.97 (s, 1H);
MS 372.18 (M+H); HPLC-Method A, Rt 2.766 min.

Example 55 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-55) :
Prepared in 30% yield. ^-HNMR (500 MHz, DMSO-d6) S 12.21
(s, 1H), 10.45 (s, 1H), 8.68 (s, 1H) , 7.89-7.45 (m, 8H) ,
6.48 (s, 1H), 0.89 (m, 2H) , 0.62 (s, 2H) . MS 396.18
(M+H) ; HPLC-Method A, Rt 3.069 min.
Example 56 (5-Methoxymethyl-2H-pyrazol-3~yl) - [2- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (IX-56) :
Prepared in 33% yield; 1HNMR (500 MHz, DMSO-d6) 5 12.51
(s, 1H), 10.48 (s, 1H), 8.60 (s, 1H) , 7.81-7.55 (m, 7H) ,
6.71 (s, 1H), 4.28 (s, 2H), 3.18 (s, 3H). MS 400.19
(M+H): HPLC-Metnod A, Rt 2.881 min.
Example 57 (lff-indazol-3-yl) - [2- (2-trifluoromethyl-
pnenyl)-quinazolin-4-yl]-amine (II-57): Prepared to
afford 51 mg (78% yield) as pale yellow solid. 1HNMR (500
MHz, DMSO-d6) 812.7 (s, 1H), 10.4 (s, 1H), 8.55 (d, 1H),
7.81 (t, 1H), 7.71 (d, 1H), 7.61 (d, 1H), 7.58 (t, 1H) ,
7.46 (m, 4H) , 7.3-6 (d, 1H) , 7.22 (t, 1H) , 6.91 (t, 1H)
ppm; LC-MS (ES+) 406.16 (M+H), (ES-) 404.19 (M-H); HPLC-
Method A, Rt 3.00 min.
Example 58 (4-Chloro-lH-indazol-3-yl)-[2-(2-
trifluoromethyl-phenyl)-quinazolin-4-yl]-amine (II-58):
Prepared in DMF (70% yield) as pale yellow solid. XHNMR
(500 MHz, DMSO-d6) 613.3 (s, br, 1H) , 10.9 (s, br, 1H),
8.60 (d, 1H) , 7.97 (t, 1H), 7.81 (d, 1H) , 7.75 (t, 1H) ,
7.67 (d, 1H), 7.63 (dd, 1H), 7.57 (m, 2H), 7.43 (d, 1H),
7.28 (dd, 1H), 7.08 (d, 1H) ppm; LC-MS (ES+) 440.10
(M+H), (ES-) 438.12. (M-H) ; HPLC-Method A, Rt 3.08 min.

Example 59 (5-Fluoro-lH-indazol-3-yl)-[2- (2-
trifluoromethyl-pnenyl) -quinazolin-4-yl] -amine (II-59) :
Prepared in DMF (34% yield) as pale yellow solid. 1HNMR
(500 MHz, DMSO-d6) 813.0 (s, 1H), 10.6 (s, 1H), 8.72 (d,
1H) , 7.99 (t, 1H),7.89 (d, 1H) , 7.79 (d, 1H) , 7.75 (t,
1H), 7.68 (m, 3H) , 7.56 (dd, 1H), 7.39 (d, 1H), 7.28 (t,
1H) ppm; LC-MS (ES+) 424.12 (M+H) , (ES-) m/e= 422.13 (M-
H) ; HPLC-Method A, Rt 3.05 min.
Example 60 (7-Fluoro-lH-indazol-3-yl)-[2- (2-
trifluoromethyl-pnenyl) -quinazolin-4-yl] -amine (II-60) :
Prepared in DMF (51% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.4 (s, 1H), 10.6 (s, 1H), 8.68 (d, 1H),
7.95 (t, 1H), 7.85 (d,-lH), 7.72 (m, 2H), 7.63. (m, 2H),
7.58 (m, 1H), 7.43 (d, 1H), 7.18 (dd, 1H), 7.00 (m, 1H)
ppm; LC-MS (ES+) 424.II (M+H), (ES-) 422.15 (M-H) ; HPLC-
Method A, Rt 3.06 min.
Example 61 (5-Methyl-lH-indazol-3-yl)-[2- (2-
trifluoromethyl-phenyl) -guinazolin-4-yl] -amine (II-61) :
Prepared in DMF (81% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.0 (s, br, 1H) , 8.79 (br, 1H) , 8.II (br,
1H), 7.96 (d, 1H) , 7.82 (m, 5H) , 7.46 (s, 1H), 7.41 (d,
1H) , 7.20 (d, 1H), 2.33 (s, 3H) ppm; MS (ES+) 420.15
(M+H), (ES-) 418.17 (M-H); HPLC-Method A, Rt 3.07 min.
Example 62 [2-(2,6-Dichloro-phenyl)-quinazolin-4-yl] -(5-
fluoro-lH-indazol-3-yl) -amine (II-62): Prepared in DMF
(37% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6)
?13.0 (s, 1H), 10.8 (s, 1H), 8.72 (d, 1H), 7.97 (t, 1H),
7.90 (d, 1H), 7.75 (t, 1H), 7.53 (m, 3H), 7.43 (t, 1H) ,
7.35 (d, 1H) , 7.23 (t, 1H) ppm; LCMS (ES+) 424.08 (M+H),
(ES-) 422.10 (M-H); HPLC-Method A, Rt 3.06 min.

Example 63 [2 - (2 -Chloro-pheny 1) -quinazolin- 4 -yl] - (lH-
indazol-3-yl) -amine (II-63): Prepared in 91% yield. 1HNMR
(500MHz, DMSO-d6) ? 7.06 (t, 1H) , 7.36 (t, 1H) , 7.39 (t,
1H), 7.52 (m, 3H), 7.62 (d, 1H), 7.72 (d, 1H), 7.82 (m,
1H), 7.90 (d, 1H), 8.05 (m, 1H), 8.76 (d, 1H), II.5 (m,
1H), 13.02 (s, 1H); EI-MS 372.1 (M+l); HPLC-Method A, Rt
2.93 min.
Example 64 (S-Trifluoromethyl-lH-indazol-3-yl)- 12-(2-
trif luoromethyl-pheny 1) -gulnazolin-4-yl] -amine (II-64) :
Prepared in DMF (57% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.4 (s, br, 1H), II.4 (br, 1H), 8.72 (d,
1H) , 8.12 (s, 1H), 7.98 (t, 1H) , 7.83 (d, 1H) , 7.76 (d,
1H), 7.73 (dd, 1H), 7.60 (m, 4H), 7.52 (d, 1H) ppm; LC-MS
(ES+) 474.12 (M+H), (ES-) 472.17 (M-H); HPLC-Method A, Rt
3.25 min.
Example 65 (4-Trifluoromethyl-lH-indazol-3-yl) - [2r (2-
trifluoromethyl-pheny 1) -quinazolxn-4-yl] -amine (II-65) :
Prepared in DMF (8% yield) as yellow solid. ^HNMR (500
MHz, DMSO-d6) 513.7 (s, br, 1H), II.2 (br, 1H), 8.70 (d,
1H) , 8.05 (s,. 1H), 7.85 (m, 3H) , 7.65 (m, 4H) , 7.51 (m,
2H) ppm; LC-MS (ES+) 474.13 (M+H), (ES-) 472.17 (M-H);
HPLC-Method A, Rt 3.15 min.
Example 66 [2-(2,6-Dichloro-phenyl)-guinazolin-4-yl] -(Uff-
indazol-3-yl)-amine (II-66): Prepared in DMF (30% yield)
as yellow solid. 1HNMR (500 MHz, DMSO-d6) 812.9 (s, 1H),
II.1 (s, 1H), 8.69 (d, 1H) , 7.95 (t, 1H)., 7.82 (d, 1H) ,
7.73 (t, 1H) , 7.56 (d, 1H) , 7.47 (s, 1H) , 7.45 (s, 1H) ,
7.39 (m, 2H), 7.26 (t, 1H), 6.92 (t, 1H) ppm; LC-MS (ES+)

406.II (M+H) , (ES-) 404.12 (M-H) ; HPLC-Method A, Rt 3.00
min.
Example 67 (lH-indazol-3-yl) - [2- (2-methyl-phenyl) -
quinazolin-4-yl] -amine (II-67) : Prepared in 55% yield.
1HNMR (500MHz, DMSO-d6) ? 2-15 (s, 3H) , 7.09 (t, 1H) , 7.26
(d, 1H), 7.31 (t, 1H), 7.39 (t, 1H), 7.42 (m, .1H), 7.55
(d 1H), 7.64 (d, 1H), 7.74 (d, lH),7.89 (m, 1H), 7.96
(d, 1H), 8.10 (m, 1H), 8.81 (d, 1H), 12.0 (m, 1H), 13.18
(s, 1H) ; EI-MS 352.2 (M+l) ; HPLC-Method A, Rt 2.93 min.
Example 68 (7-Trifluoromethyl-lH-indazol-3-yl) - [2- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-68) :
Prepared in DMF (75% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) ??13.5 (s, br, 1H) , II.2 (s, br, 1H) , 8.68
(d, 1H), 7.97 {t, 1H), 7.92 (d, 1H), 7.82 (d, 1H), 7.74
(t, 1H) , 7.70 (d, 1H) , 7.68 (d, 1H) , 7.64 (m, 2H) , 7.57
(m, 1H) , 7..14 (t, 1H) ppm; LC-MS (ES+) 474.II (M+H),
(ES-) 472.14 (M-H) ; HPLC-Method A, Rt 3.24 min.
Example 69 (6-Trifluorcmeth.yl-lH-indazol-3-yl) - [2- (2-
trif luoromethyl-phenyl) -quinazolin-4-yl] -amine (II-69) :
Prepared by Method B in DMF (78% yield) as yellow solid.
1HNMR (500 MHz, DMSO-d6) ? 13 .4 (s, br, 1H) , II.1 (s, br,
1H), 8.67 (d, 1H), 7.95 (t, 1H) , 7.82 (m, 3H), 7.72 (m,
2H), 7.63 (m, 2H) , 7.57 (t, 1H),7.23 (d, 1H) ppm; LC-MS
(ES+) 474.12 (M+H), (ES-) 472.15 (M-H); HPLC-Method A, Rt
3.28 min.
Example 70 (5-Nitro-lH-indazol-3-yl) - [2- (2-
trifluoromethyl-phenyl)-quinazolin-4-yl] -amine (II-70) :
Prepared in DMF (82% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) ?13.6 (s, br, 1H), II.4 (s, br, 1H), 8.75

(s, 1H), 8.72 (d, 1H), 8.09 (dd, 1H), 7.98 (t, 1H), 7.83
(d, 1H), 7.75 (t, 1H), 7.70 (m, 2H), 7.61 (m, 3H) ppm;
LC-MS (ES+) 451.14 (M+H) , (ES-) 449.12 (M-H) ; HPLC-Method
A, Rt 3.02 min.
Example 71 (5,7-Difluoro-lH-iadazol-3-yl)-[2-(2-
trifluoromethyl-phenyl)-quinazolin-4-yl]-amine (II-71):
Prepared in DMF (60% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.7 (s, br,. 1H) , II.2 (s, br, 1H) , 8.73
(d, 1H), 8.03 (t, 1H), 7.88 (d, 1H), 7.80 (m, 2H), 7.70
(m, 3H) , 7.32 (m, 2H) ppm; LC-MS (ES+) 442.14 (M+H), (ES-
) 440.14 (M-H); HPLC-Method A, Rt 3.II min.
Example 72 (4-Pyrrol-l-yl-lH-indazol-3-yl)-[2-(2-
trifluoromethyl-phenyl)-quinazolin-4-yl]-amine (II-72) :
Prepaxed in DMF (33% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.4 (s, br, 1H), II.0 (s, br, 1H) , 8.53
(d, 1H), 7.98 (t, 1H), 7.75 (m, 4H), 7.62 (m, 2H) , 7.52
(d, 1H), 7.43 (t, iH), 7.05 (d, 1H), 6.80 (s, 2H), 5.61
(s, 2H) ppm; LC-MS (ES+) 471.18 (M+H), (ES-) 469.18 (M-
H) ; HPLC-Method A, Rt 3.12 min.
Example 73 (5-Amino-lH-indazol-3-yl) - [2- (2-
trifluoromethyl-phenyl)-quinazolin-4-yl]-amine (II-73): A
solution of compound II-70 (70 mg, 0.16 mmol) in MeOH (2
mL) was treated with Raney Ni until solution was
colorless (about 1.5 g Raney Ni was added). After
stirring at room temperature for 40 min, the mixture, was
filtered through celite, the resulting celite was washed
with MeOH (5 times) , and the solvent was evaporated in
vacuo to provide a crude product that was then purified
by HPLC to give the title compound as a yellow solid (10
mg, 15%) . m.p. 221-223°C; 1HNMR (500 MHz, DMSO-d6)

?13.2 (s, br, 1H) , 10.7 (s, br, 1H) , 9.80 (br, 2H) , 8.68
(d, 1H), 7.97 (t, 1H), 7.87 (d, 1H) , 7.75 (m, 2H), 7.65
(m, 5H) , 7.30 (d, 1H) ppm; MS (ES+) 421.16 (M+H) , (ES-)
419.17 (M-H) ; HPLC-Method A, Rt2.41 rain.
Example 74 12- (2-Chloro-phenyl) -quinazolin-4-yl] - (7-
fluoro-lH-indazol-3-yl)-amine (II-74): Prepared in DMF
(35% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6)
?13.7 (s, 1H), II.7 (s, br, 1H), 8.80 (d, 1H) , 8.15 (t,
1H), 7.99 (d, 1H), 7.88 (t, 1H), 7.68 (d, 1H) , 7.60 (m,
2H), 7.53 (t, 1H), 7.46 (t, 1H), 7.25 (dd, 1H), 7.04 (m,
1H) ppm; LC-MS (ES+) 390.16 (M+H); HPLC-Method A, Rt 3.00
min.
Example 75 [2- (2-Chloro-phenyl) -guinazolin-4-yl] - (5-
fluoro-lH-indazol-3-yl)-amine (II-75): Prepared in DMF.
1HNMR (500 MHz, DMSO-d6) 513.2 (s, 1H) , II.7 (s, br, 1H) ,
8.80 (d, 1H), 8.10 (t, 1H) , 7.91 (m, 2H), 7.70 (d, 1H),
7.58 (m, 4H) , 7.50 (t, 1H) , 7.29 (t, 1H) ppm; LC-MS (ES+)
390.17 (M+H); HPLC-Method A, Rt 3.00 min.
Example 76 [2- (2-Chloro-phenyl) -quinazolin-4-yl] - (5,7-
difluoro-lH-indazol-3-yl) -amine (II-76) : Prepared in DMF
(55% yield) as yellow solid. 1HNMR (500 MHz, DMSO-d6)
513.8 (s, 1H) , II.5 (s, br, 1H), 8.76 (d, 1H) , 8.08 (t,
1H), 7.93 (d, 1H) , 7.84 (t, 1H), 7.64 (d, 1H) , 7.55 (d,
1H), 7.50 (t, 1H) , 7.44 (m, 2H), 7.36 (t, 1H) ppm; LC-MS
(ES+) 408.15 (M+H), (ES-) 406.17 (M-H); HPLC-Method A, Rt
3.08 min.
Example 77 [2- (2-Chloro-phenyl) -quinazolin-4-yl] - (5-
trifluoromethyl-lH-indazol-3-yl)-amine (II-77): Prepared
in DMF (66% yield) as yellow solid. 1HNMR (500 MHz, DMSO-

d6) 8.13.5 (S, 1H), II.4 (s, br, 1H) , 8.79 (d, 1H) , 8.29
(s, 1H), 8.07 (t, 1H), 7.93 (d, 1H) , 7.84 (t, 1H) , 7.72-
(d, 1H), 7.63 (d, 2H), 7.53 (d, 1H), 7.48 (t, 1H) , 7.36
(t, 1H) ppm; LC-MS (ES+) : m/e= 440.16 (M+H) ; (ES-) : m/e=
438.18 (M-H); HPLC-Method A, Rt 3.22 min.
Example 78 [2-(2-cyano-pnenyl)-quinazolin-4-yl] - (1£T-
indazol-3-yl)-amine (II-78).: Prepared in 13% yield. 1H-
NMR (500 MHz, DMSO) 8 12.9 (br, 1H) , 10.8 (br, 1H) , 8.73
(br s, 1H), 7.97 (m, 4H) , 7.74 (m, 1H), 7.5 (m, 4H), 7.42
(m, 1H) , 7.08 (m, 1H) ppm; MS (FIA) 363.2 (M+H); HPLC-
Method A, Rt 2.971 min.
Example 79 (5-Bromo-lH-indazol-3-yl) - [2- (2- . .
trifluoromethyl-phenyl) -guinazolin-4-yl] -amine (II-79) :
Prepared in DMF (64% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.4 (s, 1H) , II.6 (s, br, 1H) , 8.93 (d,
1H) , 8.21 (t, 1H) , 8.14 (s, 1H) , 8.05 (d, 1H) , 7.95 (m,
4H) , 7.86 (t, 1H), 7.65 (d, 1H), 7.59 (d, 1H) ppm; MS"
(ES+) 486.10 (M+H), (ES-) 484.09 (M-H); HPLC-Method A, Rt
3.22 min.
Example 80 (6-Cnloro-lH-indazol-3-yl) - [2- (2-
trifluoromethyl-phenyl) -guinazolin-4-yl] -amine (II-80) :
Prepared in DMF (94% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.1 (s, 1H), II.2 (s, br, 1H) , 8.73 (d,
1H) , 8.03 (t, 1H) , 7.87 (d, 1H) , 7.79 (m, 2H) , 7.73 (m,
2H) , 7.67 (m, 2H) , 7.58 (s,. 1H) , 7.04 (dd, 1H) ppm. LC-MS
(ES+) 440.14 (M+H), (ES-) 438.16 (M-H); HPLC-Method A, Rt
3.25 min.
Example 81 (7-Fluoro-6-trifluorometbyl-lff-indazol-3-yl) -
[2- (2-trifluoromethyl-pb.enyl) -quinazolin-4-yl] -amine (II-

81) : Prepared in DMF (30% yield) as yellow solid. 1HNMR
(500MHz, DMSO-d6) ?13.9 (s, 1H),-II.O (s, br, 1H), 8.64
(d, IB), 7.94 (t, 1H), 7.81 (d, 1H) , 7.71 (m, 2H) , 7.60
(m, 4H) , 7.20 (dd, 1H) ppm. LC-MS (ES+) 492.18 (M+H) ,
(ES-) 490.18 (M-H) ; HPLC-Method A, Rt 3.44 min.
E2amElS_B2_{6-Bromo-lH-indazol-3-yl) - [2- (2-
triflnoromethyl-phenyl) -quinazolin-4-yl] -amine (II-82) :
Prepared in DMF (40% yield) as yellow solid. XHNMR (500
MHz, DMSO-d6) ?13.1 (s, 1H) , II.2 (s, br, 1H) , 8.73 (d,
1H), 8.03 (t, 1H), 7.87 (d, 1H), 7.80 (m, 2H), 7.73 (m,
3H) , 7.67 (m, 1H) , 7.61 (d, 1H) , 7.15 (dd, 1H) ppm; MS
(ES+) 486.07 (M+H); HPLC-Method A, Rt 3.28 min.
Example 83 [2-(2,4-Bis-trifluoromethyl-phenyl)-
quinazolin-4-yl] - (5,7-difluoro-lff-indazol-3-yl) -amine
(II-83): Prepared in DMF in 28% yield. 1HNMR (500MHz,
MeOH-d4) ? 8.81 (d, J=8.4Hz, 1H), 8.35-8.20 (m, 3H) ,
8.19-7.96 (m, 3H), 7.40-7.34 (m, 1H), 7.29-7.14 (m, 1H) ;
LC-MS (ES+) 510.14 (M+H); HPLC-Method C, Rt 8.29 min.
Example 84 (5,7-Difluoro-lH-indazol-3-yl)-[2-(4-fluoro-2-
trifltioromethyl-phenyl) -quinazolin-4-yl] -amine (II-84) :
Prepared in 48% yield. 1HNMR (500MHz, MeOH-d4) ? 8.74-
8.63 (m, 1H) , 8.23-8.10 (m, 1H) , 7.99-7.90 (m, 2H) •, 7.89-
7.80 (m, 1H), 7.71-7.61 (m, 1H), 7.61-7.50 (m, 1H), 7.24-
7.15 (m, 1H), 7.14-7.02 (m, 1H); LC-MS (ES+) 460.14
(M+H); HPLC-Method C, Rt 7.59 min.
Example 85 [2-(2-Bromo-phenyl)-quinazolin-4-yl]-(5,7-
difluoro-lH-indazol-3-yl)-amine (II-85): Prepared in THF
(21% yield). 1HNMR (500MHz, MeOH-d4) 88.81 (d, J=8.4Hz,
1H) , 8.35-8.20 (m, 3H) , 8.19-7.96 (tn, 3H) , 7.40-7.34 (m,

1H) , 7.29-7.14 (m, 1H) ; LC-MS (ES+) 510.14 (M+H) ; HPLC-
Method C, Rt 8.29 min.
Example 86 (5,7-Difluoro-lH-indazol-3-yl) - [2- (5-fluoro-2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-86) :
Prepared in THF (26% yield) . 1HNMR (500MHz, MeOH-d4)
8 8.62 (d, J=8.4Hz, 1H) , 8.16-8.02 (m, 1H) , 7.96-7.73 (m,
3H) , 7.59-7.48 (m, 1H), 7.48-7.35 (m, 1H), 7.21-7.09 (m,
1H) , 7.09-6.89 (m, 1H); LC-MS (ES+) 460.16 (M+H); HPLC-
Method C, Rt 7.28 min.
Example 87 [2- (2,4-Dichloro-phenyl) -quinazolin-4-yl] -
(5,7-Difluoro-lH-indazol-3-yl)-amine (II-87): Prepared in
THF (16% yield). 1HNMR (500MHz, MeOH-d4) ? 8.81 (d,
J=8.4Hz, 1H) , 8.35-8.20 (m, 3H) , 8.19-7.96 (m, 3H) , 7.40-
7.34 (m, 1H), 7.29-7.14 (m, 1H); LC-MS (ES+) 510.14
(M+H); HPLC-Method C, Rt 8.29 min.
Example 88 [2- (2-Chloro-5-trifluoromethyl-phenyl)-
quinazolin-4-yl] - (5,7-Difluoro-lH-indazol-3-yl) -amine
(II-88) : Prepared in THF (33% yield) . 1HNMR (500MHz,
DMSO-d6) 8 10.76 (s, 1H), 8.66 (d, J=8.3Hz, 1H), 8.06-
7.84 (m, 3H), 7.81-7.63 (m, 3H), 7.48-7.16 (m, 2H); LC-MS
(ES+) 476.16 (M+H); HPLC-Method C, Rt 19.28 min.
Example 89 (4-Fluoro-1H-indazol-3-yl)-[2-(2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-89) :
Prepared in NMP (79% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) ?13.2 (s, 1H), 10.8 (s, br, 1H) , 8.63 (d,
1H), 7.97 (t, 1H), 7.85 (d, 1H), 7.74 (m, 2H), 7.64 (t,
1H), 7.57 (m, 2H),.7.32 (m, 2H), 6.82 (m, 1H) ppm; LC-MS
(ES+) 424.17 (M+H) ; HPLC-Method A, Rt 3.14 min.

Example 90 (1H-Indazol-3-yl) - [8-methoxy-2- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-90) :
Prepared using THF as solvent to afford the title
compound as a TFA salt (23% yield). HPLC-Method A, Rt 2.97
min (95%); 1HNMR (DMSO-d6, 500 MHz) ? 12.9 (1H, bs) , II.0
- 10.7(1H, bs) , 8.2.5 (1H, m) , 7.75-7.50 (8H, s) , 7.30
(1H, m) , 6.90 (1H, m) , 4.0 (3H, s) ; MS (m/z) 436.2 (M+H) .
Example 91 (5-Fluoro-lH-indazol-3-yl) - [8-methoxy-2- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-91) :
Prepared using TFA as solvent to afford the title
compound as a TFA salt (23% yield) . HPLC-Method A, Rt
3.10 min. (99%); 1HNMR (DMSO-d6, 500 MHz): 13.0 (1H, bs) ,
II.0 - 10.7(1H, bs) , 8.25 (1H, m) , 7.75-7.50 (7H, m) ,
7.35 (1H, m), 7.25 (1H, m), 4.0 (3H, s); MS (m/z) 454.2
(M+H) .
Example 92 (7-Fluoro-lH-indazol-3-yl) - [8-methoxy-2- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-92) :
Prepared using THF as solvent to afford the title
compound as a TFA salt (98 mg, 58% yield) . HPLC-Method
A, Rt 3.20 min (92%); 1HNMR (DMSO-d6, 500 MHz) ? 13.45
(1H, bs) , II.0 - 10.7 (1H, bs) , 8.25 (1H, m) , 7.75-7.60
(5H, m), 7.50.(1H, m), 7.40 (1H, m) , 7.15 (1H, m), 6.95
(1H, m) 4.0 (3H, s); MS (m/z) 454.2'(M+H).
Example 93 (5,7-Difluoro-lH-indazol-3-yl) - [8-methoxy-2-
(2-trif luoromethyl-phenyl) -quinazolin-4-yl] -amine (II-
93) : Prepared using THF as solvent to afford the title
compound as a TFA salt (36% yield) . HPLC-Method A, Rt
3.27 min. (95%); 1HNMR (DMSO-d6, 500 MHz): 13.65 (1H, bs) ,
II.0 - 10.7 (1H, bs), 8.22 (1H, m), 7.75-7.60 (5H, m) ,

7.40 (1H, m), 7.35 (1H, m), 7.19 (1H, m), 4.0 (3H, s); MS
(m/z) 472.2 (M+H) .
Example 94 12-(2-Chloro-pyridin-3-yl)-guinazolin-4-yl]-
{5,7-Difluoro-1H-indazol-3-yl)-amine (II-94): Prepared in
DMF. 1HNMR (500MHz, DMSO-d6) ? 13.62 (br s, . 1H, II.06-
10.71 (m, 1H), 8.16-7.70 (m, 4H), 7.60-7.09 (m, 3H); LC-
MS (ES+) 409.14 (M+H) ; HPLC-Method A, Rt 2.89 min.
Bxample 95 [2- (2-Chloro-4-nitro-phenyl) -quinazolin-4-yl] -
(5,7-dlfluoro-lH-indazol-3-yl) -amine (II-95): Prepared in
THF. 1HNMR (500MHz, DMS0-d6) ? 13.35 (s, 1H) , 10.74 (s,
1H) , 8.67 (d, J=8.4Hz, 1H), 8.29 (d, J=2.05Hz, 1H) , 8.18-
8.08 (m, 1H), 8.07-7.60 (m, 4H), 7.53-7.10 (m, 2H). LC-
MS (ES+) 453.15 (M+H); HPLC-Method D, Rt 3.63 min.
Example 96 [2-(4-Amino-2-chloro-phenyl)-quinazolin-4-yl]-
(5,7-Difluoro-lH-indazol-3-yl)-amine (II-96) :
A solution of compound II-95 (8mg, 0.018mmol) and tin
chloride dihydrate (22mg, O.lmmol) in ethanol (2mL) was
heated at 100°C for 24h. The reaction was diluted with
EtOAc (lOmL) , washed with IN NaOH solution (2xl0mL) ,
brine, and dried over anhydrous sodium sulfate to afford
the crude product!. Purification was achieved by flash
chromatography on silica gel (eluting with 1-3% MeOH in
CH2C12.) The title compound was isolated as pale yellow
solid (1.2mg, 16% yield). LC-MS (ES+) 423.12 (M+H),
HPLC-Method C, Rt 13.78 min.
Example 97 (4,5,6,7-Tetrahydro-lH-indazol-3-yl)
-[2- (2-trifluoromethyl-phenyl) -guinazolin-4-yl] -amine
{II-97) : Prepared in 34% yield. 1HNMR (500MHz, DMSO-d6) ?
1.58 (m, 2H), 1.66 (m, 2H), 2.24 (m, 2H), 2.54 (m 2H),

7.63 (m, 3H), 7.71 (t, 1H) , 7.75. (d, 1H) , 7.78 (d, 1H) ,
7.85 (t, 1H), 8.53 (d, 1H) , 9.99 (s, 1H), 12.09 (s, 1H) ;
EI-MS 410.2 (M+l) ; HPLC-Method A, Rt 3.05 min.
Example 98 (lH-Pyrazolo [4,3-b]pyridin-3-yl) - [2- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-98) :
Prepared in OMF (37% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.1 (s, br, 1H) , II.2 (s, br, 1H), 8.73
(d, 1H) , 8.54 (dd, 1H) , 8.12 (d, 1H) , 8.06 (t, 1H) , 7.90
(d, 1H) , 7.84 (t, 1H) , 7.75 (d, 1H), 7.69 (m, 2H) , 7.65
(t, 1H) , 7.47 (dd, 1H) ppm; LC-MS (ES+) 407.18 (M+H);
HPLC-Method A, Rt 2.77 min.
Example 99 (1H-Pyrazolo [3,4-b]pyridin-3-yl) - [2- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-99) :
Prepared in IMF (45% yield) . 1HNMR (500 MHz, DMSO-d6)
?13.5 (s, br, 1H), II.3 (s, br, 1H), 8.78 (d, 1H), 8.49
(d, 1H) , 8.17 (d, 1H) , 8.03 (t, 1H) , 7.89 (d, 1H) , 7.80
(m, 2H), 7.74 (m, 2H) , 7.68 (m, 1H), 7.08 (dd, lH).ppm.
MS -(ES+) 407.16 (M+H), (ES-) 405.16 (M-H) ; HPLC-Method A,
Rt.2.80 min.
Example 100 (6-Methyl-lH-pyrazolo[3,4-b]pyridin-3-yl) - [2-
(2-trif luoromethyl-phenyl) -guinazolin-4-yl] -amine (II-
100): Prepared in DMF (II% yield). 1HNMR (500 MHz, DMSO-
d6) ?13.2 (s, br, 1H) , 10.8 (s, br, 1H), 8.57 (d, 1H) ,
7.95 (t, 1H) , 7.82 (d, 1H) , 7.72 (t, 1H) , 7.65 (m, 2H) ,
7.58 (m, 2H) , 2.44 (s, 3H, buried by DMSO) , 2.20 (s, 3H)
ppm. LC-MS (ES+) 435.22 (M+H), (ES-) 433.25 (M-H); HPLC-
Method A, Rt 2.94 min.
Example 101 (6-Oxo-5-phenyl-5,6-dihydro-lH-pyrazolo[4/3-
clpyridazin-3-yl) - [2- (2 -trifluoromethyl-phenyl) -

quinazolin-4-yl] -amine II-101: Prepared in DMF (6%
yield). 1HNMR (500 MHz, DMSO-d6) ?12.6 (s, 1H) , II.0 (s,
br, 1H) , 8.60 (d, 1H) , 7.95 (t, 1H), 7.88 (d, 1H), 7.80
(d, 1H), 7.68 (m, 4H), 7.40 (s, 3H), 7.22 (s, 2H) , 6.61
(s, 1H) ppm. LC-MS (ES+) 500.21 (M+H), (ES-) 498.16 (M-
H) ; HPLC-Method A, Rt 3.00 min.
Example 103 [6-Methyl-2- (2-trifluoromethoxy-ph.enyl) -
pyrimidin-4-yl] - (5-phenyl-2H-pyrazol-3-yl) -amine (II-
103): MS 412.13 (M+H); HPLC-Method E Rt 1.248 min.
Example 104 (5-Furan-2-yl-2H-pyrazol-3-yl) - [6-methyl-2-
(2-trifluorometnoxy-phenyl) -pyrimidin-4-yl] -amine (II-
104); MS. 402.12 (M+H); HPLC-Method E, Rt 1.188 min.
Example 105 [6-Ethyl-2- (2-trifluoromethoxy-phenyl) -
pyrimidin-4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (II-
105): MS 364.14 (M+H); HPLC-Method E,' Rt 1.II2 min.
Example 106 [2- (2-Chloro-phenyl) -pyrido [2,3-d] pyrimidin-
4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (II-106): 1HNMR
(500 MHz, DMSO) ?12.23 (s, 1H) , 10.78 (s, 1H) , 7.73-7.47
(m, 7H) , 6.72 (s, 1H) , 2.21 (s, 3H). MS: (M+H) 337.02.
HPLC-Method A, Rt 2.783 min.
Example 107 (5-Fluoro-lH-indazol-3-yl) - [2- (2-
trif luoromethyl-phenyl) - 6,7 -dihydro-5H-
cyclopentapyrimidin-4-yl] -amine (II-107) : Prepared in 68%
yield. 1HNMR (500MHz, DMSO-d6) ? 2.16 (t, 2H), 2.88 (m,
2H) , 2.98 (t, 2H), 7.21 (td, 1H) , 7.29 (dd, 1H), 7.50
(dd, 1H), 7.65 (t, 1H), 7.67 (t, 1H), 7.73 (t, 1H), 7.79
(d, 1H) , 10.22 (br. S, 1H) , 12.99 (br. s, 1H) ; EI-MS
414.2 (M+H); HPLC-Method A, Rt 2.92 min.

Example 108 (1H-Indazol-3-yl)-[2-(2-trifluoromethyl-
phenyl) -pyrido[2,3-d]pyrimidin-4-yl] -amine (II-108) :
HPLC-Method A, Rt 2.78 min. (95%); 1HNMR (DMSO-d6, 500
MHz): 12.95 (1H, bs) , II.45 5 II.15(1H, bs) , 9.20 (2H,
m), 7.85-7.70 (2H, m), 7.70-7.55 (4H, m) , 7.50 (1H, m),
7.35 (1H, m), 7.05 (1H, m); MS (m/z) 407.03 (M+H).
Example 109 (5,7-Difluoro-lH-indazol-3-yl) - [2- (2-
trifluoromethyl-phenyl) -pyrido [2,3-d]pyrimidin-4-yl] -
arnine (II-109) : Yellow, di-TFA salt (25% yield) . HPLC
(Method A) 3.10 min. (95%); 1HNMR (DMSO-d6, 500 MHz) :
13.8-13.6 (1H, bs), II.4 - II.2(1H, bs), 9.15 (2H, m),
7.85-7.75 (2H, m) , 7.75-7.62 (3H, m) , 7.32 (2H, m) ; MS
(m/z) 442.98 (M+H).
Example II0 [2- (2-Chioro-phenyl) -pyrido [2,3-d] pyrimi din -
4-yl] -{1H-indazol-3-yl) -amine (II-II0)i Prepared from 2-
aminonicotinic acid and 2-chlorobenzoyl chloride afforded
the title compound as a di-TFA salt (28% yield) . HPLC-
Method A, Rt 2.85 min. (95%); 1HNMR (DMSO-d6, 500 MHz):
12.90 (1H, s), II.10 - 10.90 (1H, bs), 9.05 (2H, m),
7.75-7.60 (2H, m) , 7.51 (1H, m) , 7.45-7.25 (5H, m) ,6.95
(1H, m); MS (m/z) 372.99(M+H).
Example III (5-Fluoro-lH-indazol-3-yl) - [2-(2-
trifluoromethyl-phenyl) -5,6,7,8,9,10-heacahydro-
eyclooctapyrimidin-4-yl]-amine (II-III). Prepared in 43%
yield. 1HNMR (500MHz, DMSO-d6) 8 1.46 (m, 2H) , 1.53 (m,
2H) , 1.77 (m, 4H) , 2.95 (m, 2H) , 3.04 (m, 2H) , 7.22 (m,
2H), 7.50 (dd, 1H), 7.72 (m, 3H) , 7.80 (d, 1H) , 10.5 (m,
1H) , 13.05 (br S, 1H) ; El-MS 456.2 (M+H); HPLC-Method C,
Rt II.93 min.

Example II2 [2- (2-Chloro-phenyl) -6,7-dihydro-5H-
cyclopentapyrimidin-4-yl] - (5-fluoro-1H-indazol-3-yl) -
amine (II-II2) : Prepared in 67% yield. 1HNMR (500MHz,
DMS0-d6) ?2.18 (m, 2H), 2.89 (m, 2H) , 3.02 (t, 2H) , 7.24
(td, 1H), 7.42 (m, 2H), 7.49 (td, 1H) , 7.52 (dd, 1H) ,
7.54 (d, 1H) , 7.57 (dd, 1H) , 10.50 (br. s, 1H) , 13.06
(br. s, 1H) ; EI-MS 380.1 (M+l) ; HPLC-Method C, Rt 9.68
min.
Example II3 (lH-Indazol-3-yl) - [2- (2-trifluoromethyl-
phenyl) -6,7-dihydro-5H-cyclopentapyrimidin-4-yl] -amine
(II-II3) : Prepared in 37% yield. 1HNMR (500MHz, DMSO-d6)
5 2.65 (m, 2H), 2.85 (m, 2H), 2.99 (t, 2H) , 7.02 (t, 1H) ,
7.32 (t, 1H), 7.47 (d, 1H), 7.55 (d, 1H), 7.68 (t, 1H) ,
7.74 (t, 1H), 7.80 (d, 1H), 10.37 (br. s, 1H) , 12.91 (br.
S, 1H); EI-MS 396.1 (M+H); HPLC-Method B, Rt 9-88 min.
Example II4 (7-Fluoro-lH-indazol-3-yl)-[2-(2-
trifluoromethyl -phenyl) -6,7- dihydro - 5H-
cydopentapyrimidin-4-yl]-amine (II-II4): Prepared in 40%
yield. 1HNMR (500MHz, DMSO-d6) ? 2.15 (m, 2H) , 2.87 (m,
2H), 2.97 (t, 2H), 6.99 (td, 1H), 7.17 (dd, 1H), 7.38 (d,
1H), 7.65 (m, 2H), 7.71 (t, 1H) , 7.78 (d, 1H), 10.21 (br.
S, 1H), 13.40 (br. s, 1H); EI-MS 414.1 (M+H); HPLC-Method
C, Rt 9.99 min.
Example II5 (5,7-Difluoro-lH-indazol-3-yl) - [2- (2-
trifluoromethyl-phenyl) -6,7-dihydro-5H-
cyclopentapyrimidin-4-yl]-amine (II-II5): Prepared
according to Method C in 52% yield. 1HNMR (500MHz, DMSO-
d6) ? 2.16 (m, 2H), 2.89 (m, 2H) , 2.97 (t, 2H),.7.19 (dd,
1H) , 7.29 (td, 1H) , 7.63 (t, 1H), 7.66 (d, 1H), 7.71 (t,

1H), 7.78 (d, 1H), 10.16 (br. s, 1H) , 13.55 (br. s, 1H) ;
El-MS 432.1 (M+H); HPLC-Metnod C, Rt 10.09 min.
Example II6 [2- (2-Chloro-pnenyl) -6,7-dihydxo-5H-
cyclopentapyrimidin-4-yl] - (lH-indazol-3-yl) -amine (II-
II6) : Prepared in 56% yield. 1HNMR (500MHz, DMSO-d6)
? 2.16 (m, 2H) , 2.85 (m, 2H) , 3.01 (t, 2H) , 7.06 (t, 1H) ,
7.34 (t, 1H), 7.40 (t, 1H), 7.48 (m, 2H) , 7.53 (d, 1H) ,
7.56 (d, 1H), 7.63 (d, 1H), 10.39 (br. S, 1H), 12.91 (s,
1H) ; El-MS 362.1 (M+H); HPLC-Method A, Rt 3.09 min.
Example II7 [2-(2-Chloro-phenyl)-6,7-dihydro-5H-
cyclopentapyrimidin-4-yl] - (7-fluoro-lH-indazol-3-yl) -
amine (II-II7) : Prepared in 63% yield. 1HNMR (500MHz,
DMSO-d6) ? 2.15 (m, 2H) , 2.87 (m, 2H) , 3.00 (t, 2H) , 7.01
(td, 1H), 7.19 (dd, 1H) , 7.39 (t, 1H) , 7.45 (m, 2H), 7.51
(d, 1H), 7.55 (d, 1H) , 10.35 (br. s, 1H), 13.45 (br. s,
1H) ; EI-MS 380.1 (M+H); HPLC-Method A, Rt Rt 3.15 min.
Example II8 [2-(2-Chloro-ph.enyl)-6,7-dihydxo-5H-
cydopentapyrimidin-4-yl] - (5,7-difluoro-lH-indazol-3-yl) -
amine (II-II8) : Prepared in 60% yield. 1HNMR (500MHz,
DMSO-d6) 6 2.18 (m, 2H) , 2.91 (m, 2H) , 3.01 (t, 2H) , 7.32
(t, 1H) , 7.33 (td, 1H) , 7.41 (t, 1H), 7.48 (t, 1H) , 7.53
(d, 1H) , 7.55 (dd, 1H), 10.35 (br. s, 1H), 13.45 (br. s,
1H) ; EI-MS 398.1 (M+H); HPLC-Method A, Rt Rt 3.24 min.
Example II9 (lff-Indazol-3-yl) - [2- (2-trifluoromethyl-
pbenyl) -S, 6,7, 8,9,10-hexahydro-cyclooctapyrimidin-4-yl] -
amine (II-II9) : Prepared in 36% yield. 1HNMR (500MHz,
DMSO-d6) 5 1.47 (m, 2H), 1.53 (m, 2H) , 1.78 (m, 4H), 2.96
(m, 2H), 3-06 (t, 2H) , 7.03 (t, 1H), 7.47 (t, 1H), 7.72
(d, 1H) , 7.73 (d, 1H), 7.72 (m, 3H), 7.81 (d, 1H),.1O.52

(m, 1H) ,. 12.97 (br. s, 1H) ; EI-MS 438.2 (M+l) ; HPLC-
Method A, Rt 3.37 min.
Example 120 (7-Fluoro-lH-indazol-3-yl)-[2- (2-
trifluoromethyl-phenyl)-5,6,7,8,9,10-hexahydro-
cyclooctapyrimidin-4-yl]-amine (II-120): Prepared in 40%
yield. 1HNMR (500MHz, DMSO-d6) ? 1.46 (m, 2H) , 1.52 (m,
2H), 1.77 (m, 4H), 2.94 (m, 2H), 3.04 (m, 2H) , 7.00 (td,
1H), 7.17 (dd, 1H), 7.30 (d, 1H) , 7.70 (m, 3H), 7.79 (d,
1H), 10.5 (m, 1H), 13.49 (br s, 1H); EI-MS 456.1 (M+H);
HPLC-Method A, Rt 3.43 min.
Example 121 (5,7-Difluoro-lH-indazol-3-yl) - [2- (2-
trifluoromethyl-phenyl)-5,6,7,8,9,10-hexahydro-
cyelooctapyrimidin-4-yl]-amine (II-121): Prepared in 48%
yield. 1HNMR (500MHz, DMSO-d6) ? 1.46 (m, 2H) , 1.52 (m,
2H), 1.77 (m, 4H), 2.95 (m, 2H), 3.03 (m, 2H) , 7.14 (d,
1H) , 7.30 (t, 1H), 7.73 (m, 3H), 7.80 (d, 1H) , 10.5 (m,
1H) , 13.62 (br. S, 1H) ,- EI-MS 475.1 (M+l); HPLC-Method A,
Rt 3.52 min.
Example 122 [6-Cyclohexyl-2 - (2 -trifluoromethyl-phenyl) -
pyrimidin-4-yl] - (lH-indazol-3-yl)-amine (II-122):
Prepared in 45% yield. 1HNMR (500 MHz, CDC13) ? 1.30 (2H,
m), 1.46 (2H, m), 1.65 (2H, m) , 1.76 (2H, m) , 1.91 (2H,
m), 2.61 (1H, br m), 7.08 (1H, t, J=7.4 Hz), 7.27' (1H, d,
J=8.0 Hz), 7.35 (1H, t, J= 7.1 Hz), 7.50 (1H, t, J=7.0
Hz), 7.58 (1H, t, J=7.4 Hz), 7.66 (3H, m) , 7.72 (1H, d,
J=7.8 Hz), 8.0 (1H, br), 9.87 (1H, br) ppm; HPLC-Method
D, Rt 3.57 min; LC-MS 438.17 (M+H) +
Example 123 [6-(2-Fluoro-phenyl)-2- (2-trifluoromethyl-
phenyl) -pyrimidin-4-yl] - (lH-indazol-3-yl) -amine (IX-123) :

Prepared in 8% yield. 1HNMR (500 MHz, CDCl3) 8 7.18
(3H, m) , 7.37 (1H, m), 7.43 (1H, t,. J=7.9 Hz), 7.51 (1H,
d, J=7.9 Hz), 7.55 (IE, t, J=7.6 Hz), 7.65 (1H, t, J=7.4
Hz), 7.79 (1H, d, J=7.9 Hz), 7.85 (1H, d, J= 7.6 Hz),
8.19 (2H, m) , 8.70 (1H, d, J= 8.5 Hz) ppm; HPLC-Method D,
Rt 4.93.min; LC-MS 450.13 (M+H)+
Example 124 (6-Fluoro-lH-indazol-3-yl) - 12- (2-
trifluoromethyl-phenyl) -quinazolin-4-yl] -amine (II-124) .
Prepared in DMF (87% yield) as yellow solid. 1HNMR (500
MHz, DMSO-d6) 813.0 (s, 1H) , II.1 (s, br, 1H), 8.66 (d,
1H), 7.95 (t, 1H) , 7.80 (d, 1H),.7.72 (m, 2H), 7.62 (m,
4H) , 7.21 (dd, 1H), 6.84 (td, 1H) ppm. LC-MS (ES+) 424.15
(M+H); HPLC-Method A, Rt 3.05 min.
Example 125 3- [2~.(2-Tri£luoromethyl-plienyl) -quinazolin-4-
ylamino] -lH-indazole-5-carboxylic acid methyl ester (II-
125) : To a solution of compound II-79 (100 mg 0.21 mmol)
in DMF (2 mL) was added MeOH (1 mL) , DIEA (54 uL, 0.31
mmol) and PdCl2(dppf) (4 mg, 0,005 mmol). The flask was
flushed with CO three times and then charged with a CO
balloon. The reaction mixture was heated at 80°C for 14
h then poured into water. The resulting precipitate was
collected and washed with water. The crude product was
then purified first by flash column (silica gel, 50%
• ethyl acetate in hexanes) then by preparative HPLC to to
afford II-125 (32%) as yellow solid. 1HNMR (500 MHz,
DMSO-d6) 813.3 (s, 1H), II.3 (s, br, 1H) , 8.70 (d, 1H) ,
8.36 (s, 1H) , 7.97 (t, 1H) , 7.82 (m, 2H) , 7.71 (m, 3H) ,
7.58 (m, 2H) , 7.51 (d, 1H) , 3.75 (s, 3H) ppm; LC-MS (ES+)
464.13 (M+H); HPLC-Method A, Rt 3.12 min.

Example 208 (5-Methyl-2H-pyrazol-3-yl) - [2- (2-naphthyl-l-
yl) -qu.inazolin-4-yl] -amine (II-208): 1HNMR (500 MHz, DMSO-
6.6) ? 8.92 (s, 1H), 8.73 (m, 1H) , 8.39 (m, 1H) , 8.09 (m,
2H), 7.95 (m, 3H), 7.62 (m, 3H), 6.78 (s, 1H), 2.32 (s,
3H); MS 352.2 (M+H).
Example 209 [2- (2-Chloro-phenyl) -pyrido [2,3-d] pyrimidin-
4-yl] - (7-fluoro-lff-indazol-3-yl) -amine (II-214) : Prepared
from 4-Chloro-2- (2-cnloro-phenyl) -pyrido[2,3-d]pyrimidine
(100 mg, 0.36mmol) and 7-Fluoro-lH-indazol-3-ylamine
(108mg, 0.72mmol). Purification by preparative HPLC
afforded the title compound as a yellow, di-TFA salt (93
mg, 46% yield). HPLC-Method A, Rt 3.04 min; 1H NMR (DMSO,
500 MHz): ? 13.67 (1H, s), II.40-II.25 (1H, bs), 9.35-
9.25 (2H, m) , 7.95 (1H, m) , 7.80-7.47 (5H, m) , 7.-35 (1H,
m) , 7.15 (1H, m); MS (m/z), MH+ 391.1.
Example 210 [2- (2-Chloro-pbenyl) -pyrido [2,3-d]pyrimidin-
4-yl] - (5-fluoro-lH-indazol-3-yl)-amine (II-215): Prepared
from 4-Chloro-2- (2-chloro-phenyl) -pyrido[2,3-d]
pyrimidine (100 mg, 0.36mmol) and 5-Fluoro-lJ?-indazol-3-
ylamine (108mg, 0.72mmol). Purification by preparative
HPLC afforded the title compound as a yellow, di-TFA salt
(45 mg, 22% yield). HPLC-Method A, Rt 3.00 min; XH NMR
(DMSO, 500 MHz): 8 13.0 (1H, s) , 10.90 (1H, bs) , 9.15-9.05
(2H, m) , 7.70 (1H, m) , 7.60-7.30 (6H, m), 7.20 (1H, m);
MS (m/z), MH* 391.1.
Example 2II [2- (2-Chloro-phenyl) -pyrido [2,3-d]pyrimidin-
4-yl] - (5,7-di£luoro-lH-indazol-3-yl) -amine (II-216) :
Prepared from 4-Chloro-2-(2-chloro-phenyl)-pyrido [2, 3-
d]pyrimidine (100 mg, 0.36mmol) and 7-Difluoro-1H-
indazol-3-ylamine, (II2mg, 0.66mmol) . Purification by

preparative HPLC afforded the title compound as a yellow,
di-TFA salt (130 mg, 62% yield). HPLC-Method A, Rt 3.12
min; lH NMR (DMSD, 500 MHz): 13.80-13.60 (1H, bs) , II.30-
II.10 (1H, bs), 9.20-9.10 (2H, m) , 7.80 (1H, m), 7.60-
7.30 (6H, m); MS (m/z) , MH4 409.1.
Example 212 [2- (2-Chloro-ph.enyl) -pyr±do[3,4-d]pyrimidin-
4-yl]- (lff-indazol-3-yl)-amine (II-217): Prepared from 4-
C!hloro-2- (2-chloro-phenyl) -pyrido [3, 4-d] pyrimidine (100
mg, 0.36mmol) and lH-indazol-3-ylamine (88mg, 0.66mmol)
Purification by preparative HELC afforded the title
compound as a yellow, di-TFA salt (72 mg, 33% yield) .
HPLC-Method A, Rt 3.21 min;. ^H NMR (DMSO, 500 MHz) : 8
12.95 (1H, s), 10.90 (1H, bs), 9.25 (1H, s), 8.75 (1H,
m), 8.55 (1H, m) , 7.65 (1H, m), 7.55 (1H, m), 7.50-7.30
(5H, m) , 7.00(1H, m) ; MS (m/z), MH+ 373.1.
Example 213 [2- (2-Cliloro-phenyl) -pyridoI3,4-d]pyrimidin-
. 4-yl] - (7-fluoro-lff-inda2ol-3-yl)-amine (II-218): Prepared
from 4-Chloro-2- (2-chloro-phenyl) -pyrido [3,4-d]pyrimidine
(100 mg, 0.36mmol) and 7-Fluoro-lH-indazol-3-ylamine
(108mg, 0.72mmol). Purification by preparative HPLC
afforded the title compound as a yellow, di-TFA salt
(48.7 mg, .22% yield). HPLC-Method A, Rt 3.35 min; *B. NMR
(DMSO, 500 MHz): 5 12.95 (1H, s) , 10.90 (1H, bs) , 9.25
(1H, s), 8.75 (1H, m) , 8.55 (1H, m) , 7.70-7.35 (5H, m) ,
7.25(1H, m) , 6.95 (1H, m) , ; MS (m/z), MH+ 391.08.
Example 214 [2- (2-Chloro-phenyl) -pyrido [3,4-d]pyrimidin-
4-yl]-(5-fluoro-lH-indazol-3-yl) -amiae (II-219) : Prepared
from 4-chloro-2- (2-chloro-5-fluoro-lH-indazol-3-ylamine
(108mg, 0.72mmol). Purification by preparative HPLC.
afforded the title compound as a yellow, di-TFA salt

(57.2 mg, 26% yield) . HPLC-Method A, Rt 3.27 min; 1H NMR
(DMSO, 500 MHz): ? 13.05 (1H, s), 10.95 (1H, s), 9.25
(1H, s), 8.75 (1H, m) , 8.55 (1H, m) / 7.60 (1H, m), 7.55
(1H, m) , 7.50-7.30 (5H, m) , 7.25 (1H, m) ; MS (m/z) , MH+
391.1.
Example 215 [2 - {2 -Chloro-pheny 1) -pyrido [3,4- d] pyr imidin-
4-yl] - (5,7-difluoro-lff-indazol-3-yl) -amine (II-220) :
Prepared from 4-chloro-2- (2-chloro-7-difluoro-lH-indazol-
3-ylamine (II2mg, 0.66mmol). Purification by preparative
HPLC afforded the title compound as a yellow, di-TFA salt
(57.2 mg, 26% yield). HPLC-Method A, Rt 3.45 min; 1H NMR
(DMSO, 500 MHz): ? 13.65 (1H, s), II.0 (1H, s), 9.25 (1H,
s) , 8.80 (1H, m) , 8.50 (1H, m) , 7.60 (1H, m) , 7.55 (1H,
m), 7.50-7.30 (5H, m); MS (m/z), MH+ 409.1.
Example 216 6-Fluoro-lH-indazol-3-ylamine (Al) : 1HNMR
(500 MHz, DMSO-d6) ?II.4 (s, 1H) , 7.68 (dd, 1H) , 6.95
(dd, 1H), 6.75 (td, 1H), 5.45 (s, 2H) ppm; LC-MS (ES+)
15-2.03 (M+H) ; HPLC-Method A, Rt 2.00 min.
Example 217 5-Fluoro-lH-indazol-3-ylamine (A2) : 1HNMR
(500 MHz, DMSO-d6) 8II.3 (s, 1H) , 7.43 (d, 1H) , 7.22 (m,
1H) , 7.08 (m, 1H) , 5.29 (s, 2H) ppm; LC-MS (ES+) 152.01
(M+H); HPLC-Method A, Rt 1.93 min.
Example 218 5,7-Difluoro-lH-indazol-3-yl-anine (A3) : 1HNMR
(500 MHz, CD3OD) ?7.22 (dd, J=2.0, 8.45HZ, 1H) , 7.04-6.87
(m, 1H) ; LC-MS (ES+) 169.95 (M+H); HPLC-Method C, Rt 2.94
min
Example 219 7-Fluoro-lH-indazol-3-ylamine (A4) : 1HNMR (500
MHz. DMSO-d6) ?II.8 (s, 1H) , 7.42 (d, 1H) , 6.97 (m, 1H) ,

6.78 (m, 1H) , 5.40 (s, 2H) ppm;- LCMS (ES+) 152.01 (M+H) ;
HPLC-Method A, Rt 2.00 min.
Example 220 7 -Fluoro- 6-trifluoromethyl - 1H-indazol- 3 -
ylamine (A5) : 1H-NMR (500 MHz, DMSO) 5 12.5 (s, 1H), 7.75
(d, 1H) , 7.25 (m, 1H) , 5.85 (m, 1H) ppm; MS (FIA) 220.0
(M+H); HPLC-Method A, Rt 2.899 min.
Example 221 6-Bromo-lH-indazol-3-yleuiLine (A6) : 1H-NMR (500
MHz, DMSO) ? II.5 (s, 1H) , 7.65 (d, 1H) , 7.40 (s,. 1H) ,
7.00 (d, 1H) , 5.45 (br S, 1H) ppm; MS . (FIA) 213.8 (M+H);
HPLC-Method A, Rt 2.441 min.
Example 222 4-Fluoro-lH-indazol-3-ylamine (A7) : 1H-NMR
(500MHz, DMSO) ? II.7 (s, 1H), 7.17 (m, 1H), 7.05 (d,
1H) , 6.7 (br, 1H), 6.60 (dd, 1H), 5.20 (br s, 2H) ppm; MS
(FIA) 152.0 (M+H); Method A, Rt 2.256 min.
Example 223 5-Bromo-lH-indazol-3-ylamine (A8) : 1H-NMR (500
MHz, DMSO) 8 II.55 (br s, 1H) , 7.95 (s, 1H) , 7.30 (d,
1H), 7.20 (d, 1H) , 5.45 (br s, 2H) ppm; MS (FIA) 213.8
(M+H); Method A, Rt 2.451 min.
Example 224 5-Nitro-1H-indazol-3-ylamine (A9) : 1H-NMR (500
MHz, DMSO-d6) 8 9.00 (s, 1H) , 8.20 (d, 1H), 7.45 (d, 1H),
6.15 (br s, 1H) ppm; Method A, Rt 2.184 min
Example 225 4-Pyrrol-1-yl-lH-indazol-3-ylamine (A10) : XH-
NMR (500 MHz, DMSO) 8 7.20 (s, 2H) , 7.00 (s, 2H), 6.75
(m, 1H), 6.25 (s, 2H), 4.30 (d, 1H) ppm; Method A, Rt
2.625. min.

Example 226 4-Cnloro-5,6-dimethyl-2- (2-trifluoromethyl-
phenyl) -pyrimidine (Bl) : Prepared to afford a colorless
oil in 75% yield. 1H-NMR (500 MHz, CDC13) 8 7.70 (d,
J=7.8 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.55 (t, J=7.6 Hz,
1H) , 7.48 (t, J=7.5 Hz, 1H) , 2.54 (s, 3H) , 2.36 (s, 3H)
ppm; MS (FIA) 287.0 (M+H) ; HPLC-Method A, Rt 3.891 min.
Example 227 4-Cnloro-2- (2-chloro-phenyl) -5, 6-dimethyl-
pyrimidine (B2) : Prepared to afford a yellow-orange oil
in 71% yield. ^-NMR (500 MHz, CDC13) 5 7.73 (m, 1H) ,
7.52 (m, 1H) , 7.39 (m, 2H), 2.66 (s, 3H) , 2.45 (s, 3H)
ppm; MS (FIA) 253.0 (M+H); HPLC-Method A, Rt Rt 4.156 min.
Example 228 4-Chloro-6-methyl-2-(2-trifluorometby1-
plxenyl)-pyrimidine (B3) : Prepared to afford a pale yellow
oil in 68% yield. aH-NMR (500 MHz, CDC13) 5 7.72 (d,
J=7.8 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.57 (t, J=7.5 Hz,
1H), 7.52 (t, J=7.8 Hz, 1H), 7.16 (s, 1H) , 2.54 (s, 3H)
ppm; MS (FIA) 273.0 (M+H); HPLC-Method A, Rt 3.746 min.
Example 229 4-Cnloro-6-cyclohexyl-2- (2-trifluoromethyl-
phenyl) -pyrimidine (B4) : Prepared to afford a yellow oil
in 22% yield. ^-NMR (500 MHz, CDC13) 8 7.70 (m, 2H) ,
7.57 (t, J=7.5 Hz, 1H) , 7.50 (tt J=7.5 Hz, 1H), 7.19 (s,
1H), 2.65 (m, 1H), 1.9 (m, 2H), 1.8 (m, 2H), 1.5 (m, 2H) ,
1.3 (m,-2H), 1.2 (m, 2H) ppm; MS (FIA) 341.0 (M+H).
Example 230 4-Cnloro-6-pnenyl-2-(2-trifluoromethyl-
phenyl) -pyrimidine (B5) : Prepared to afford a yellow oil
in 53% yield. '"H-NMR (500 MHz, CDC13) 8 8.08 (dd, J=7.9,
1.6 Hz, 2H) , 7.80 (d, J=7.6 Hz, 1H), 7.77 (d, J=7.8 Hz,
1H) , 7.67 (s, 1H) , 7.61 (t, J=7.5 Hz, 1H) , 7.54 (t, J=7.6

Hz, 1H), 7.47 (m, 3H) ppm; MS (FIA) 335.0 (M+H) ; HPLC-
Method A# Rt 4.393 min.
Example 231 4-Chloro-2- (2,4-dichloro-phenyl) -5,6-
dimethyl-pyximidine (B6) : Prepared to afford a white
solid in 91% yield. ^-NMR (500 MHz, CDC13) 5 7.62 (d,
J=8.3 Hz, 1H), 7.43 (d, J=7.0 Hz, 1H), 7.27 (dd, J=8.3,
2.0 HZ, 1H) , 2.55 (s, 3H), 2.35 (s, 3H) ppm; MS (FIA)
287, 289 (M+H); HPLC-Method A, Rt 4.140 min.
ExaaQjle_23_2_ 4-Cliloro-6- (2-chloro-phenyl) -2- (2-
trifluorometbyl-phenyl)-pyrimidine (B7) : Prepared to
affod a yellow oil in -52% yield. ^-NMR (500 MHz, CDC13)
5 7.75 (m, 3H), 7.65 (m, 2H), 7.53 (m, 1H), 7.44 (m, 1H),
7.36 (m, 2H) ppm; MS (FIA) 369.1 (M+H); HPLC-Method A, Rt
4.426 min.
Example 233 4-Ch3oro-6-(2-fluoro-phenyl)-2-(2-
trifluoromethyl-phenyl) -pyrimidine (B8) : Prepared to
afford a yellow oil in 95% yield. ^fl-NMR (500 MHz, CDC13)
5 8.24 (t, J=7.9 Hz, 1H), 7.84 (s, 1H) , 7.78 (d, J=7.7
Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.60 7.53 (t, J=7.6 Hz, 1H) , 7.43' (m) 1H), 7.23 (t, J=7.6 Hz,
1H) , 7.13 (m, 1H) ppm; MS (FIA) 353.0 (M+H).
Example 234 4-Chloro-6-pyridixi-2-yl-2-(2-trifluoromethyl-
phenyl) -pyrimidine (B9) : Prepared to afford a pale yellow
solid in 50% yield: ^-NMR (500 MHz, CDC13) 8 8.68 (m,
1H) , 8.48 (dd, J=7.9,-0.8 Hz, 1H), 8.38 (d, J=2.3 Hz,
1H) , 7.84 (m, 3H), 7.62 (t, J=7.6 Hz, 1H), 7.55 (t, J=7.6
Hz, 1H), 7.38 (m, 1H) ppm; MS (FIA) 336.0 (M+H); HPLC-
Method A, Rt 4.575 min.

Example 235 6-Benzyl-4-chloro-2- (2-trifluoromethyl-
phenyl) -5, 6,7, 8-tetrahydro-pyrido [4,3-d]pyrimidine (BIO) :
1HNMR (500 MHz, CDC13) 5 7.. 70 (d, 1H) , 7.62 (d, 1H) , 7.55
(t, 1H), 7.48 (t, 1H), 7.32 (m, 4H), 7.25 (m, 1H) , 3.74
(s, 2H), 3.66 (s, 2H), 2.99 (t, 2H), 2.80 (t, 2H) ppm;
LCMS (ES+) 404.17 (M+H) ; HPLC-Method A, Rt 3.18 min.
Example 236 7-Benzyl-4-chloro-2- (2-trifluoromethyl-
phenyl)-5,6,7,8-tetrahydro-pyrido [3,4-d]pyrimidine (Bll) :
1HNMR (500 MHZ, CDC13) 8 7.69 (d, 1H) , 7.60 (d, 1H) , 7.54
(t, 1H), 7.47 (t, 1H), 7.28 (m, 4H), 7.20 (m, 1H) , 3.68
(s, 2H), 3.67 (s, 2H), 2.86 (t, 2H) , 2.79 (t, 2H) ppm. MS
(ES+) 404.18 (M+H); HPLC-Method A, Rt 3.12 min.
Example 237 4-Cliloro-2- (4-£luoro-2-trifluoromethyl-
phenyl)-guinazoline (B12) : 1HNMR (500MHz, CD3OD) 5 8.43
(d, J=8.1Hz, 1H) , 8.20-8.05 (m, 2H), 8.05-7.82 (m, 2H),
7.71-7.51 (m, 2H) . LC-MS (ES+) 327.09 (M+H). HPLC-Method
D, Rt 4.56 min.
Example 238 4-Chloro-2- (2-ehloro-5-trif luoromethyl-
phenyl)-guinazoline (B13): LC-MS (ES+) 342.97 (M+H).
HPLC-Method D, Rt 4.91 min.
Example 23 9 4-Chloro-2- (2-cliloro-4-nitro-phenyl) -
quinazoline (B14) : LC-MS (ES+) 319.98 (M+H). HPLC-Method
D, Rt 4.45 min.
Example 240 4-Chloro-2- (2-trifluoromefchyl-phenyl) -
guinazoline (B15) : Prepared in 57% yield. White solid.
1HNMR (500MHz, DMSO-d6) 8 7.79 (t, 1H) , 7.86 (t, 1H) , 7.94
(m, 3H) , 8.15 (dd, 1H)., 8.20 (td, 1H) , 8.37 (m, 1H) ; EI-
MS 308.9 (M).

Example 241 4-Chloro-2-(2-trifluoromethyl-phenyl) - 6,7 -
dihydro - SB- cyelopentapyr i mi dine (B16) : Prepaxed in 22%
yield. 1HNMR (500MHz, DMSO-d6) 8 2.19 (m, H) , 3.01 (t,
2H), 3.08 (t, 2H), 7.49 (t, 1H), 7.55 (t, 1H), 7.62 (d,
1H), 7.71 (d, 1H). EI-MS 299.0 (M+H).
Example 242 4-Chloro-2- (2-cliloro-phenyl) -6,7, 8,9-
tetrahydro-EH-cycloheptapyrimidine (B17) : Prepared
according to Method C in 82% yield to afford a white
solid. 1HNMR (500MHz, CDC13) 8 1.67 (m 4H) , 1.87 (m 2H) ,,
3.02 (m 4H), 7.28 (m, 2H), 7.40. (1, 1H), 7.65 (m, 1H);
EI-MS 293.0 (M+l).
Example 243 4-Chloro-2- (2 -trif luoromethyl -phenyl) -
5, 6,7, 8,9,10-hexahydro-cyclooctapyrimidine (B18) :
Prepared in 38% yield to afford a brown oil. 1HNMR
(500MHz, CDCI3) 8 1.35 (m 2H) , 1.41 (m 2H) , 1.76 (m 4H) ,
2.96 (m, 4H), 7.48 (t, 1H), 7.56 (t, 1H),.7.66 (d, 1H),
7.70 (d, 1H) ; EI-MS 341.0 (M+l).
Example 244 4-Chlbro-8-methoxy-2- (2-trifluoromethyl-
phenyl)-guinazoline (B19) : Prepared from 8-methoxy-2-(2-
trif luoromethyl-phenyl) -3H-quinazolin-4-one (1. Og,
3.12mmol), triethylamine hydrochloride (472mg, 3.43mmol),
and POCI3. Purification by flash chromatography afforded
a white solid (89% yield) . HPLC-Method A, Rt 4.10 min,
(98%), MS (m/z) 258.08 (M+H).
Example 245 2- (4-Chloro-c[uinazplin-2-yl) -benzonitrile
(B20) : Prepared to afford a yellow solid in 1.5% yield.
^-NMR (500 MHz, CDC13) 5 8.47 (d, 1H), 8.24 (d, 1H), 8.16
(d, 1H) , 8.07 (impurity), 7.94 (t, 1H) , 7.92 (impurity),

7.86 (d, 1H), 7.68 (m, 2H), 7.65 (impurity), 7.54
(impurity), 7.49 (t, 1H) , 4.2 (impurity), 1.05 (impurity)
ppm; MS (LC/MS) 266.05 (M+H) ; HPLC-Method A, Rt 3.88 min.
Example 246 6-Methyl-2-(2-trifluorometliyl-phenyl)-3H-
pyrimidin-4-one (D3): Prepared to afford a yellow solid
in 50% yield. ^H-NMR (500 MHz, DMSO-d6) 8 12.7 (br s,
1H), 7.9 (m, 1H), 7.8 (m, 2H), 7.7 (m, 1H), 6.3 (s, 1H) ,
2.21 (s, 3H) ppm; MS (FIA) 255.0 (M+H); HPLC-Method A, Rt
2.578. min.
Example 247 6-Cyclohexyl-2- (2-trif luoromethyl-phenyl) -3H-
pyrimidin-4-one (D4): Prepared to afford an off-white
solid in 54% yield. ^-NMR (500 MHz, DMSO-d6) 8 12.9 (br
s, 1H), 7.9 (m, 4H), 6.3 (s, 1H), 2.5 (m, 1H), 1.9 (m,
5H) , 1.4 (m, 5H) ppm; MS (FIA) 323.1 (M+H); HPLC-Method
A, Rt 3.842 min.
Example 248 2- (2-Chloro-5-trifluorometh.yl-phenyl) -3H-
quinazoli-4-one (D10): XHNMR (500MHz, CD3OD) 8 8.32-8.25
(m, 1H), 8.01 (s, 1H), 7.91-7.72 (m, 1H) , 7.66-7.55 (m,
1H) . LC-MS (ES+) 325.01 ' (M+H) . HPLC-Method D, Rt 3.29
min.
Example 249 2-{4-Fluoro-2-trifluoromethyl-phenyl)-3H-r
qainazolin-4-one (D14) : ^-HNMR (500MHz, CU3OD) 8 8.28 (d,
8.0HZ, 1H) , 7.94-7.84 (m, 1H) , 7.84-7.77 (m, 1H), 7.76-
7.67 (in, 2H), 7.65-7.53 (m, 2H) . LC-MS (ES+) 309.06
(M+H). HPLC-Method D,Rt 2.88 min.
Example 250 2-(4-Nitro-2-chloro-phenyl)-3H-quinazolin-4-
one (D15): LC-MS (ES+) 302.03 (M+H). HPLC-Method D, Rt
2.81 min.

Example 251 2- (5-Fluoro-2-trif luorome thyl-phenyl) -3ff-
quinazolin-4-one (D17) : XHNMR (500MHz, CD3OD) 8 8.28 (d,
Rt J=8.05Hz, 1H), 7.96 (dd, J=5.05, 8.55HZ, 1H), 7.89 (t,
J=7.9Hz, 1H) , 7.78-7.69 (m,lH), 7.66-7.46 (m, 3H). LC-MS
(ES+) 309.14 (M+H) . HPLC-Method D, Rt 2.90 min.
Example 252 (lH-Indazol-3-yl) - (2-phenyl-quinazolin-4-yl) -
amine (III-l) : Prepared by Method A in DMF to afford 70.
mg (50% yield) as pale yellow solid. XK NMR (500 MHz,
DMSO-d6) 513.1 (s, br, 1H) , 8.48 (d, 1H), 7.91 (d, 2H) ,
7.76 (br, 2H), 7.45 (m, 2H), 7.36 (d, 1H), 7.20 (m, 4H) ,
6.86 (t, 1H) ppm. MS (ES+) 338.07 (M+H); (ES-) 336.II (M-
H) ; HPLC-Method A, Rt 2.88 min.
Example 253 (5-Methyl-2H-pyrazol-3-yl) - (2-phenyl-5, 6,7, 8-
tetrahydroquinazolin-4-yl) -amine (III-7) : Prepared
according to Method A. *H NMR (500 MHz, DMSO-d6) S12.1
(s, br, 1H), 8.70 (s, br, 1H), 8.37 (d, J = 6.7 Hz, 2H),
7.54 (m, 3H), 6.67 (s, 1H), 2.82 (m, 2H), 2.68 (m, 2H) ,
2.37 (s, 3H), 1.90 (s, br, 4H) ; MS 306.1 (M+H).
Example 254 (5-Methyl-2H-pyrazol—3-yl) - (2-phenyl-6,7, 8,9-
tetrahydro-5ff-cyeloheptapyrimidin-4-yl) -amine (III-8) : MS
320.48 (M+H); HPLC-Method E, Rt 1.124 min.
Example 255 (5-Methyl-2H-pyrazol-3-yl) - (2-pyridin-4-yl-
qu.inazolin-4-yl)-amine (III-9) : Yellow solid, rap 286-
289°C, ^-H NMR (DMSO) S 2.35 (3H, s), 6.76 (1H, s) , 7.61
(1H, m), 7.89 (2H, m) , 8.32 (2H, d) , 8.70 (1H, d) , 8.78
(2H, d), 10.56 (1H, br s), 12.30 (1H, br s) ; IR (solid)
1620, 1598, 1571, 1554, 1483, 1413, 1370, 1328; MS 303.2
• (M+H)+

Example 256 (7-Chloro-2-pyridin-4-yl-quinazolin-4-yl) - (5-
methyl-2H-pyrazol-3-yl) -amine (III-28) : 2H NMR (DMSO-d6) 5
2.35 (3H,s), 6.75 (1H, s) ,. 7.65 (1H, d) , 7.93 (1H, s) ,
8.30 (2H, d), 8.73 (1H, d), 8.79 (2H, d) , 10.69 (1H, s) ,
12.33 (1H, s) ;. MS m/z 337.2 (M+H)+.
Example 257 (6-Chloro-2-pyridin-4-yl-quinazolin-4-yl)- (5-
methyl-2H-pyrazol-3-yl) -amine (III-29) : ^H NMR (DMSO-d6) 5
2.31 (3H, a); 6.74 (lH,s), 7.89 (1H, s) , 8.30 (2H, d) ,
8.80 (2H, d) , 8.91 (1H, s) , 10.63 (1H, s) , 12.29 (1H, s) ;
MS 337.2 (M+H)+.
Example 258 (2-Cydohexyl-quinazolin-4-yl)-(5-methyl-2H-
pyrazol-3-yl)-amine (III-30) : JH NMR (DMSO) 6 2.35 (3H,
s), 1.70 (3H, m), 1.87 (2H, d), 1.99 (2H, d), 2.95 (1H,
t), 6.72 (1H, s), 7.75 (1H, d), 7.88 (1H, s) , 7.96 (1H,
s) , 8.83 (1H, s) , II.95 (1H, s) , 12.70 (1H, s) ; MS 308.4
(M+H) + .
Example 259 (5-Methyl-2H-pyrazo 1 -3 -yl) - (2-phenyl-
quinazolin-4-yl)-amiae (III-31) : mp 246°C; lH NMR (400MHz)
5 2.35 (3H, s), 6.70 (1H, br s), 7.51-7.57 (4H, mj, 7.83-
7.84 (2H, d) , 8.47-8.50 (2H, d), 8.65 (1H, d) , 10.4 (1H,
s), 12.2 (1H, bs); IR (solid) 369«, 3680, 2972, 2922,
2865; MS 302.1 (M+H)+.
Example 260 [2-(4-Iodophenyl)-quinazolin-4-yl]-(5-methyl-
2H-pyfazol-3-yl)-amine (III-32) : XH 3SIMR (DMSO-d6) 5 2.34
(3H, s), 6.72 (1H, s), 7.56 (1H, d), 7.84 (2H, d), 7.93
(2H, d) , 8.23 (2H, d) , 8.65 (1H, s) , 10.44 (1H, s) , 12.24
(1H, s); MS 428.5 (M+H)+.

Example 261 [2- (3,4-Dichlorophenyl) -quinazolin-4-yl] - (5-
methyl-2H-pyrazol-3-yl) -amine (III-33) : A suspension of
2- (3,4-dichloro-phenyl) -3H-quinazolin-4-one (1g, 3.43
mmol) in phosphorus oxychloride (4 inL} was stirred at
II0°C for 3 hours. The solvent was removed by evaporation
and the residue is treated carefully with cold aqueous,
saturated NaHCO3. The resulting solid was collected by
filtration and washed with ether to afford 4-chloro-2-
(3,5-dichloro-phenyl) -quinazoline as a white solid (993
mg, 93%). To the above compound (400mg, 1.29 mmol) in
THF (30 mL) was added 3-amino-5-methyl pyrazole (396 mg,
2.58 mmol) and the resulting mixture heated at 65°C
overnight. The solvents were evaporated and the residue
triturated with ethyl acetate, filtered, and washed with
the minimum amount of ethanol to afford compound III-33
as a white solid (3II mg 65%) -. mp 274°C; XK NMR (DMSO) 5
2.34 (3H, s), 6.69 (1H, s), 7.60 (1H, m), 7.84 (1H, d) ,
7.96 (2H, d) , 8.39 (1H, dd) , 8.60 (1H, d) ,' 8.65 (1H, d) ,
10.51 (1H, s), 12.30 (1H, s); IR (solid) 1619, 1600,
1559, 1528, 1476, 1449, 1376, 1352, 797, 764, 738; MS
370.5 (M+H)+.
Example 262 [2- (4-Bromophenyl)-quinazolin-4-yl]-(5-
methyl-2H-pyrazol-3-yl)-amine (III-34): mp 262-265°C; aH
NMR (DMSO) 5 2.34 (3S, s), 6.73 (1H, s) , 7.55 (1H, m) ,
7.74 (2H, d),.7.83 (2H, m) , 8.40 (2H, d), 8.65 (1H, d) ,
10.44 (1H, s) , 12.25 (1H, S.) ; IR (solid) 1603, 1579,
1546, 1484, 1408, 1365; MS 380.1/382.1 (M+H)+.
Example 263 [2-(4-Chlorophenyl)-quinazolin-4-yl]-(5-
methyl-2H-pyrazol-3-yl)-amine (IIX-35) : mp >300°C; 1H NMR
(DMSO) 8 2.34 (3H, s), 6.74 (1H, s), 7.53-7.62 (3H, m) ,
7.84 (2H, d), 8.47 (2H, d), 8.65 (1H, d), 10.44 (1H, s) ,

12.26 (1H, s) ; IR (solid) 1628, 1608, 1584, 1546, 1489,
1408, 1369., II69; MS 336.2 (M+H) + .
Example 264 [2- (3,5-Dichlorophenyl) -guinazolin-4-yl] - (5-
metbyl-2Jy-pyrazol-3-yl)-amine (III-36) : mp 228°C; 1H NMR
(DMSO) ? 2.34 (3H, s) , 6.69 (1H, s) , 7.96 (1H, d) , 8.21
(3H, m), 8.56 (1H, d) , 8.60 (2H, d) , 10.51 (1H, s), 12.30
(1H, S) ; IR (solid) 1546, 1331, 802, 763, 729, 658, 652;
MS 370.5 (M+H)+.
Example 265 [2- (4-Cysnophenyl) -quinazolin-4-yl] - (5-
methyl-2H-pyrazol-3-yl)-amine (III-37) : mp 263°C; lH NMR
(DMSO) 8 2.34 (3H, s) , 6.72 (1H# s) , 7.61 (1H, d), 7.88
(2H, S), 8.04 (2H, d) , 8.63 (2H, d) , 8.67 (1H, s), 10.52
(1H, S), 12.27 (1H, s) ; IR (solid) 1739, 1436, 1366,
1229, 1217; MS 327.2 (M+H)+.
Example 266 [2- (3-Iodophenyl) -guinazolin-4-yl] - (5-methyl-
2H-pyrazol-3-yl)~amine (III-38) : mp 234-235°C; 1H NMR
(DMSO) ? 2.35 (3H, s), 6.73 (1H, s) , 7.35 (1H, m) , 7.56
(1H, m) , 7.85 (3H, m), 8.47 (1H, m) , 8.65 (1H, m) , 8.86
(1H, s), 10.49 (1H, s), 12.28 (1H, br s) ; IR (solid)
1560, 1541, 1469, 1360; MS 428.1 (M+H)+.
Example 267 [2- (4-Ethylsulfanylphenyl) -guinazolin-4-yl] -
(5-methyl-2ff-pyrazol-3-yl)-amine (III-39) : mp 229-231°C;
XH NMR (DMSO) 8 1.29 (3H, t), 2.35 (3H, s) , 3.07 (2H, q),
6.76 (1H, S), 7.43 (2H, d) , 7.51 (1H, m), 7.81 (2H, m),
8.41 (2H, d), 8.64 (1H, d) , 10.38 (1H, s), 12.24 (1H, br
s) ; IR (solid) 1587, 1574, 1555, 1531, 1484, 1412, 1369;
MS 362.1 (M+H)+.

Example 268 (5-Cyelopropyl-2H-pyrazol-3-yl) - (2-phenyl-
quinazolin-4-yl) -amine (III-40) : mp 218-219°C; 1H NMR
(DMS0-d6) ? 0.70-0.80(2H, m) , 0.90-1.00 (2H, m), 6.70
(1H, s), 7.45-7.55 (4H, m) , 7.80-7.85 (2H, m) , 8.45-8.55
(2H, m), 8.65 (1H, d), 10.40 (1H, s), 12.27 (1H, s); IR
(solid) 1624, 1605, 1591, 1572, 1561, 1533, 1479, 1439,
1419, 1361, 1327, 997, 828, 803, 780, 762, 710; MS 328.2
(M+H) *.
Example 269 [2- (4-tert-Butylphenyl) -guinazolin-4-yl] - (5-
methyl-2H-pyrazol-3-yl) -amine (III-41) : mp >300°C; 1H NMR
(DMS0-d6) ? 1.35 (9H, s) , 2.34 (3H, s), 6.79 (1H, s) ,
7.55 (3H, d) , 7.85 (2H, d), 8.39 (2H, d), 8.62 (1H, d) ,
10.35 (1H, s), 12.22 (1H, s); IR (solid) 1603, 1599,.
1577, 1561, 1535, 1481, 1409, 1371, 1359, 998, 841, 825,
766, 757; MS 358.3 (M+H)+.
gxample 270 [2- (4-Chloropbenyl) -quinazolin-4-yl] - (5-
cyclopropyl-2H-pyrazol-3-yl)-amine (III-42) .; ^ NMR (DMSO-
d6) 8 0.77 (4H, br m) ,2.05 (1H, m), 6.59 (1H, s), 7.60
(1H, d), 7.85 (2H, d), 7.91 (2H, d), 8.22 (2H, d), 8.65
(1H, S), 10.51 (1H,S), 12.33 (1H,S); MS 362.1 (M+H)+.
Example 271 (2-Benzo[l,3Jdioxol-5-yl-quinazolin-4-yl) - (5-
methyl-2H-pyrazol-3-yl)-amine (III-43) : XH NMR (DMSO) 8
2.33 (3H, s), 6.13 (2H, s) , 6.78 (lH,s), 7.II (1H, d),
7.80 (1H, t), 7.94 (1H, s) , 8.09 (3H, m), 8.25 (1H, d),
10.34 (1H, s) , 12.21 (1H, s) ; MS 346.5 (M+H)+.
foeample 272 [2- (4-Dimethylaminopnenyl) -quinazolin-4-yl] -
(5-methyl-2ff-pyrazol-3-yl) -amine (IXI-44) : aH NMR (DMSO-
d6) 8 2.02 (6H, s), 2.39 (3H, s), 6.83 (1H, s), 7.71 (1H,

d), 7.98 (2H, s), 8,04 (2H, d), 8.33 (2H, d), 8.67 (1H,
S), II.82 (1H, s), 12.72 (1H, s); MS 345.3 (M+H)+.
Example 273 [2- (3-Methoxyphenyl) -guinazolin-4-yl] - (5-
methyl-2JJ-pyrazol-3-yl)-amine (III-45) : mp 226°C; JH MR
(DMSO) 8 2.34 (3H,S), 3.92 (3H, s), 6.72 (1H, s), 7.21
(1H, d), 7.57 (1H, t) , 7.79 (1H, t), 8.02 (3H, m), 8.14
(1H, s), 8.79 (1H, d), 10.39 (lH,s), 12.22 (1H, s) ; IR
(solid) 1599, 1572, 1538, 1478, 1427, 1359, 833, 761,
661; MS 332.2 (M+H) + .
Example 275 (5-CyclQpropyl-2ff-pyrazol-3-yl)-[2-(3,4-
dichlorophenyl)-quinazolin-4-yl]-amine (lil-46): ^H NMR
(DMSO-d6) 8 0.86 (2H, d) , 1.02 (2H, d), 1.69 (1H, m),
6.56 (1H, s), 7.57 (1H, d), 7.84 (4H, m) , 8.40 (1H, d) ,
8.58 (1H, s), 8.64 (1H, s) , 10.53 (1H, s), 12.36 (1H, s) ;
MS 396.0 (M+H)+.
Example 276 (2-Bipnenyl-4-yl-quinazolin-4-yl) - (5-methyl-
2fl--pyrazol-3-yl)-aiuine (III-47) : .To a mixture of 12-(4-
bromo-phenyl) -quinazolin-4-yl] - (5-methyl-2H-pyrazol-3-
yl)-amine (IIX-34) (196 mg, 0.51 mmol) and phenylboronic
acid (75 mg, 0.62 mmol) in THF:water (1:1, 4 mL) vra.s
added Na2CO3 (219 mg, 2.06 mmol), triphenylphosphine (9mg,
1/15 mol%) and palladium acetate (1 mg, 1:135 mol%). The
resulting mixture was neated at 80°C overnight, the
solvents were evaporated and the residue purified by
flash chromatography (gradient of dichloromethane:MeOH)
to afford III-21 as a yellow solid {99 mg, 51%): aH NMR
(DMSO) 8 2.37 (3H, s), 6.82 (1H, s), 7.39-7.57 (4H, m),
7.73-7.87 (6H, m), 8.57 (2H, d), 8.67 (1H, d), 10.42 (1H,
s), 12.27 (1H, s); MS 378.2 (M+H)+.

Example 277 [2- (4-Ethyaylphenyl) -quinazolin-4-yi] - (5-
methyl-2ff-pyrazol-3-yl)-aniine (III-48) : To a mixture of
[2- (4-bromo-phenyl) -quinazolin-4-yl] - (5-methyl-2ff-
pyrazol-3-yl)-amiae (III-34) (II4 mg, 0.3 mrnol) , and
trimethylsilylacetylene (147 mg, 1.5 mmol)in DMF (2 mL)
was added Cul (1.1 mg, 1:50 mol%) , Pd(PPh.3)2Cl2 (4.2 mg,
1:50 mol%) and triethylamine (121 mg, 0.36 mmol) . The
resulting mixture was heated at 120°C overnight and the
solvent evaporated. The residue was triturated in ethyl
acetate and the resulting precipitate collected by
filtration. The collected solid was suspended in THF (3
mL) and TBAF (1M in THF, l.leq) was added. The reaction
mixture was stirred at room temperature for 2 hours and
the solvent evaporated. The residue was purified by
flash chromatography (silica gel, gradient of DCM:MeOH)
to afford III-48 as a white solid (68 mg, 70%): XH NMR
.(DMSO) 6 2.34 (3H, s) , 4.36 (1H, s) , 6.74 (1H, s) , 7.55
(1H, m) , 7.65 (2H, d) , 7.84 (2H, m) , 8.47 (2H,. d) , 8.65
(1H, d), 10.43 (1H, s), 12.24 (1H, s) ; MS 326.1 (M+H)+.
Example 278 [2- (3-Ethynylphenyl) - quinazolin-4-yl] - (5-
methyl-2ff-pyrazol-3-yl)-amine {XII-49) : mp 204-207°C; *H
NMR (DMSO) 8 2.34 (3H, s) , 4.28 (1H, s) , 6.74 (1H, s) ,
7.55-7.63 (3H, m), 7.83-7.87 (2H, m) , 8.49 (1H, d) , 8.57
(1H, S), 8.65 (1H, d), 10.46 (1H, s), 12.27 (1H, s) ; IR'
(solid).1598, 1574, 1541, 1489, 1474, 1422, 1365; MS
326.1 (M+H)+.
Example 279 [2- (3-Methylphenyl) -guiaazolin-4-yl] - (5-
methyl-2B'-pyrazol-3-yl) -amine (III-50) : A suspension of
lH-quinazoline-2,4-dione (10.0 g, 61.7 mmol) in POC13 (60
mL, 644 mmol) and N,N-dimethylani.line (8mL, 63^1 nrniol)
was heated under reflux for 2 h. The excess POCl3 was .
300

removed in vacuo, the residue poured into ice, and the
resulting precipitate collected by filtration. The crude
solid product 2,4-dichloro-quinazoline {6.5 g, 53% yield)
was washed with water and dried under vacuum for next
step use without further purification. To a solution of
the 2,4-dichloro-quinazqline (3.3 g, 16.6 mmol) in
anhydrous ethanol (150 mL) was added 5 -methyl-l.ff-pyrazol-
3-yl amine (3.2 g, 32.9 mmol) and the resulting mixture
was stirred at room temperature for 4 hours. The
resulting precipitate was collected by filtration, washed
with ethanol, and dried under vacuum to afford 4.0 g (93%
yield) of (2-chloro-quinazolin-4-yl) - (5-methyl-lJ?-
pyrazol-3-yl) -amine which was used in the next step
without further purification. To a solution of the (2-
chloro-quinazolin-4-yl) - (5-methyl-l.ff-pyrazol-3-yl) -amine
(50 mg, 0.19 mmol) in DMF (1.0 mL) was added m-tolyl
boronic acid (0.38 mmol), 2M Na2CO3 (0.96 mmol) , and tri-
t-butylphosphine (0.19 mmol). The flask was flushed with
nitrogen and the catalyst. PdCl2(dppf) (0.0II mmol) added
in one portion. The reaction mixture was then heated at
80°C for 10 hours, cooled to room temperature, and poured
into water (2 mL) . The resulting precipitate was
collected by filtration, washed with water, and purified
by HPLC to afford III-50 as a pale yellow solid (61mg,
75%): XH NMR (500 MHz, DMSO-d6) 812.3 (br s, 1H) , 10.4
(br s, 1H), 8.75 (d, 1H), 8.30 (s, 1H), 8.25 (d, 1H) ,
7.78 (s, 2H), 7.55 (m, 1H), 7.45 (m, 1H) , 7.35 (m, 1H),
6.80 (s, 1H), 2.47 (s, 3H), 2.30 (s, 3H) ; MS 316.1.(M+H).
Example 280 [2- (3, 5-Difluorophenyl) -quinazolin-4-yl] - (5-
methyl-2H-pyrazol-3-yl) -amine (III-51): 1H NMR (500 MHz,
DMSO-dS) ?12.3 (br s, 1H) , 10.8. (br s, 1H) , 8.63 (d, 1H) ,

7.95 (d, 2H), 7.85 (m, 2H) , 7.58 (t, 1H) , 7.41 (t, 1H) ,
6.59 (s, 1H) , 2.27 (s, 3H) ; MS 338.1 (M+H) .
Example 281 [2- (3-Chloro-4-fluorophenyl) -quinazolin-4-
yl]-(5-methyl-2H-pyrazol-3-yl)-amine (III-52) : 2H NMR (500
MHz, DMSO-d6) ?12.4 (br s, 1H) , 10.8 (br s, 1H) , 8.65 (d,
1H), 8.50 (d, 1H) , 8.36 (m, 1H), 7.85 (m, 1H) , 7.60 (m,
1H), 6.62 (s, 1H), 2.30 (s, 3H) ; MS 354.1 (M+H).
Example 282 (5-Methyl-2H-pyrazol-3-yl) - [2- (3-
trifluoromethylphenyl) -guinazolin-4-yl] -amine (III-53) : 1H
NMR (500 MHz, DMSO-d6) 812.2 (br, 1H) , 10.45 (br, 1H) ,
7.53 (s, 1H) , 7.43 (d, J = 7.2 Hz, 1H) , 7.06 (d, J = 8.2
Hz, 1H) , 6.65 (d, J = 8.3 Hz, 1H), 6.57 (t, J = 7.6 Hz,
1H) , 6.51 (d, J = 7.8 Hz, 1H), 6.43 (t, J = 7.8 Hz, 1H),
6.32 (t, J = 7.6 Hz, 1H), 5.51 (s, 1H) , 2.03 (s, 3H); MS
370.2 (M+H) .
Example 283 [2- (3-Cyanophenyl) -guinazolin-4-yl] - (5-
methyl-2£r-pyrazol-3-yl)-amine (III-54) : XH NMR (500 MHz,
DMSO-d6) 59.01 (s, 1H) , 8.96 (m, 2H) , 8.28 (d, J= 7.3
HZ, 1H), 8.16 (S, br, 2H), 8.06 (t, J = 7.8 Hz, 1H), 7.88
(m, IB), 6.96 (S, 1H), 2.58 (s, 3H); MS 327.1 (M+H).
Example 284 [2- (3-Isopropylph.enyl) -quinazolin-4-yl] - (5-
methyl-2ff-pyrazol-3-yl) -amine (III-55) : hi NMR (500 MHz,
DMSO-d6) 8 8.89 (d, J = 7.5 Hz, 1H) , 8.37 (s, 1H)', 8.26
(s, 1H) , 8.08 (m, 2H) , 7.81 (t, br, 1H) , 7.67 (m, 2H) ,
6.88 (s, 1H), 3.12 (m, 1H), 2.40 (s, 3H), 1.38 (d, J =
6.9 Hz, 6H) ; MS 344.2 (M+H).
Example 285 (5-Methyl-2H-pyrazol-3-yl) - (2-pyridin-3-yl-
guinazolin-4-yl)-amine (III-56) : TH NMR (500 MHz, DMSO-d6)

89.50 (s, 1H) , 8.84 (d, J = 7.3 Hz, 1H) , 8.80 (d, J = 4.4
Hz, 1H) , 8.66 (d, J = 8.2 Hz, 1H) , 7.87 (m, 2H) , 7.77 (tn,
1H), 7.60 (t, J =7.2 Hz, 1H) , 6.67 (s, 1H) , 2.28 (s,
3H) ; MS 303.1 (M+H) .
Example 286 [2- (3-Acetylphenyl) -quinazolin-4-yl] - (5-
HLethyl-2H-pyrazol-3-yl)-amine (III-57): XH NMR (500 MHz,
DMSO-d6) 5 8.80 (s, 1H) , 8.55 (d, J = 7.7 Hz, 1H), 8.42
(d, J = 7.6 Hz, 1H), 8.00 (d, J = 7.0 Hz, 1H), 7.76 (m,
2H) , 7.58 (t, J = 7.7 Hz, 1H), 7.48 (s, br, 1H), 6.60 (s,
1H), 2.49 (s, 3H) , 2.03 (s, 3H) ,- MS 344.1 (M+H).
Example 287 12- (3,5-Ditrifluoromethylphenyl) -quinazolin-
4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (III-58) : lH NMR
(500 MHz, DMSO-d6) 610.7 (s, br, 1H) , 8.95 (s, 2H) , .8.63
(d, J = 8.2 Hz, 1H), 8.25 (s, 1H) , 7.86 (m, 2H), 7.58 (t,
J = 6.9 Hz, 1H), 6.62 (s, 1H), 2.26 (s, 3H) ; MS 438.1
(M+H) .
Example 288 [2- (3-Hydroxymethylphenyl) -guinazolin-4-yl] -
{5 -methyl - 2JI-pyrazol- 3 -yl) - amine (III-59) : :H MMR (500
MHz, DMSO-d6) S 8.74 (d, J = 7.9 Hz, 1H) , 8.33 (s, 1H) ,
8.17 (s, br, 1H), 7.95 (s, br, 1H) , 7.89 (s, br, 1H),
7.62 (m, 3H), 6.72 (s, 1H) , 5.53 (s, 1H), 4.60 (s, 2H) ,
2.28 (s, 3H); MS 332.1 (M+H).
Example 289 (5-Methyl-2Hr-pyrazol-3-yl) - [2-(3-
phenoxyphenyl) -quinazolin-4-yl] -amine (III-60) : mp 231-
232°C; XH NMR (DMSO-d6) 8 2.21 (3H, s) , 6.59 (1H, s) ,
7.10-7.22 (4H, m), 7.41-7.45 (2H, m) , 7.54-7.59 (2H, m),
7.81 (2H, S), 8.09 (1H, s), 8.27 (1H, m) , 8.64 (1H, m),
10.40 (1H, s)', 12.20 (1H, s) ; IR (solid); IR (solid)
1589, 1560, 1541, 1536, 1484, 1360, 1227; MS 394.7 (M+H)+.

Example 290 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (3-
pheaoayphenyl)-quiaazolia-4-yl]-amiae (III-61) : mp 193-
195°C; XH NMR (DMSO-d6) 5 0.67 (2H, m) , 0.93 (2H, m),1.87
(lH,m), 6.56 (1H, s), 7.06-7.20 (4H, m), 7.40-7.43 (2H,
m), 7.55-7.59 (2H, m) , 7.81 (2H, s) , 8.II (1H, s), 8.27
. (1H, m), 8.63 (OH, m) , 10.43 (1H, s) , 12.26 (1H, s); IR
(solid); IR (solid) 1589, 1574, 1527, 1483, 1369, 1226;
MS 420.7 (M+H)+.
Example 291 (5-Metayl-2S-pyrazol-3-yl) - (2-taiophen-3-yl-
guinarolin-4-yl)-amine (III-62): aH NMR (500 MHz, DMSO-d6)
8II.78 (s, br, 1H), 8.75 (d, J = 8.1 Hz, 1H), 8.68 (s,
1H), 7.98 (dd, J = 7.9, 7.5 Hz, 1H) , 7.89 (m, 2H),.7.81
(m, 1H) , 7.68 (t, J = 7.5 Hz, 1H), 6.69 (s, 1H) , 2.30 (s,
3H); MS 308.1 (M+H).
Example 292 (2-Phenyl-quinazolin-4-yl) - (2fl'-pyrazol-3-yi) -
amine (III-63): mp 247-249°C; XH NMR (DMSO) 8 6.99 (1H, br
s), 7.49-7.58 (5H, m) , 7.81 (1H, brs), 7.83 (2H, m) ,
8.47-8.49 (2H, m) , 8.66 (1H, d), 10.54 (1H, s), 12.59
(1H, S) ; IR (solid) 3145, 2922, 1622, 1597; MS 288.2
(M+H) + .
Example 293 (2H-Pyrazol-3-yl) - (2-pyridin-4-yl-quinazblin-
4-yl)-amine (XII-64):.mp 285-286°C; ^ NMR (DMSO) 8 6.99
(1H, brs), 7.65 (1H, m), 7.81-7.94 (3H, m) , 8.3-8.35
(2H, m), 8.73 (1H, d) , 8.84-8.90 (2H, m) , 10.76 (1H, s),
12.6 (1H, s); IR (solid) 3180, 2972, 1600, 1574; MS 289.2
(M+H)pxample 294 ,5-Ethyl-2H-pyrazol-3-yl) - (2-paenyl-
quiaazolia-4-yl)-amine (III-65): mp 221-222°C; *H NMR

(DMSO) 5 1.31 (3H, t) , 2.-68 (2H, d) , 6.80 (1H, s) , 7.50-
7.60 (4H, m), 8.45-8.55 (2H, m), 8.65-8.75 (1H, m), 10.44
(lH,s), 12.27 (lH,s); IR (solid) 3190, 1622, 1595, 1575,
1533, 1482, 1441, 1420, 1403, 1361, 758, 7II; MS 316.2
(M+H)+.
Example 295 (2-Phenyl-quinazolin-4-yl) - (5-propyl-2H-
pyrazol-3-yl)-amine (III-66) : mp 204-205°C; 1H NMR (DMSO-
d6) 8 1.02 (3H, t), 1.66-1.75 (2H, m), 2.69 (2H, t), 6.80
(1H, s), 7.45-7.60 (4H,m), 7.80-7.88 (2H, m), 8.45-8.50
(2H, m), 8.65 (1H, d) , 10.39 (1H, s) , 12.25 (1H, s) ; IR
(solid) 1621, 1560, 1572, 1533, 1479, 1441, 1421, 1363,
1328, 999, 827, 808, 763, 709, 697; MS 330.2 (M+H)+.
Example 296 (5-Isopropyl-2ff-pyrazol-3-yl) - (2-phenyl-
quinazolin-4-yl)-amine (III-67) : mp 218-219°C; XH NMR
(DMSO-d6) 8 1.36 (6H, d) , 3.05 (1H, m) , 6.86 (1H, s),
7.48-7.59 (4H, m), 7.80-7.88 (2H, m) , 8.49-8.58 (2H, m) ,
8.66 (1H, d), 10.47 (1H, s), 12.30 (1H, s); IR (solid)
3173, 2968, 1619, 1593, 1573, 1533, 1478, 1438, 1413,
1398, 1363, 1329, 995, 822, 798, 761, 707, 666, 659; MS
330.2 (M+H)+.
Example 297 (5-tert-Butyl-2ff-pyrazol-3-yl) - (2-phenyl-
guinazolin-4-yl) -amine (III-68) : mp 136-137°C; XH NMR
(DMSO-d6) 8 1.38 (9H, s), 6.87 (1H, br s), 7.51-7.57 (4H,
m) , 7.84-7.85 (2H, m) , 8.49-8.51 (2H, tn) , 8.65 (1H, d) ,
10.43 (1H, S), 12.21 (1H, br s); IR (solid) 3162, 2963,
1621, 1590, 1572; MS 344.2(M+H)+.
Example 298 (5-tert-Butyl-2H-pyrazol-3-yl) - (2-pyridin-4-
yl-quinazolin-4-yl) -amine (III-69) : mp >300°C; 1H NMR
(DMSO) ? 1.38 (9H, s) , 6.82 (1H, brs), 7.63 (1H, m),

7.86-7.91 (2H, m), 8.32-8.33 (2H, d), 8.69 (1H, d),
8.75-8.76 (2H, d) , 10.60 (1H, s), 12.31 (1H, br s); IR
(solid) 3683, 3149, 2963, 1621; MS 345.2(M+H)+.
Example 299 (5-Cyclopentyl-2ir-pyrazol-3-yl) - (2-phenyl-
qiiinazolin-4-yl)-amine (III-70): mp 240-241°C; ^ NMR
(DMSO-d6) 8 1.68-1.89 (6H, m), 2.03-2.17 (2H, m), 3.14-
3.22 [1H, m) , 6.80 (1H, s) , 7.50-7.60 (4H, m), 7.80-7.89
(2H, n) , 8.45-8.52 (2H, m) , 8.67 (1H, d) , 10.52 (1H, s) ,
12.26 (1H, s); IR (solid) 2957, 1621, 1591, 1571, 1531,
1476, 1438, 1405, 1370, 1325, 999, 951, 801, 775, 761,
747, 710695, 668, 654; MS 356.2(M+H)+.
Example 300 (5-Phenyl-2H-pyrazol-3-yl) - (2-plxenyl-
quinazolin-4-yl)-amine (III-71) : mp 207-209°C; aH NMR
(DMSO) 5 7.38-7.40 (1H, m), 7.50-7.58 (6H, m), 7.82-7.88
(4H, m) , 8.51 (2H, m) , 8.67 (1H, s), 10.58 (1H, s), 13.II
(1H, br s) ; IR (solid) 3345, 3108, 1627, 1612; MS 364.2
(M+H)Example 301 (5 - Carboxy- 2ff-pyrazol - 3 -yl) - (2 -plxenyl -
guinazolin-4-yl)-amine (III-72) : (5-Methoxycarbonyl-2.ff-
pyrazol-3-yl) - (2-phenyl-quinazolin-4-yl) -amine .(IIX-73)
(345mg, 1 mmole in THF, 6 mL) was treated witb NaOH (1M,
4.0 mL), stirred at 50°C for 5 hours, cooled to room
temperature, and neutralised with. 1M HC1. The mixture
was concentrated in vacuo to remove THF then diluted witb
water and the resulting precipitate filtered. The
.residual solid was dried at 80°C under vacuum to afford
III-72 as an off-white solid (312 mg, 94%) : mp 289-.291°C
(dec); ^-H NMR (DMSO) 5 7.45 (1H, br s) , 7.50-7.60 (5H,
m), 7.80-7.88 (2H, m) , 7.40-7.50 (2H, m), 8.60-8.70 (1H,
d), 10.70 (1H, s) , 13.00-13.80 (2H, br s); IR (solid)

16.99, 1624, 1607, 1570,1539, 1506, 1486, 1398, 1333,
1256, II77, 1004, 827, 764, 705; MS 332.3 (M+H)+.
Example 3 02 (5-Methnxycarbonyl-2H-pyrazol-3-yl) - (2-
phenyl-quinazolin-4-yl) -amine (III-73) : rap 271-273 °C; 1H
NMR (DMSO)6 3.95 (3H, s) , 7.50-7.65 (5H, m) , 7.80-7.98
(2H, m) , 8.40-8.50 (2H, m) , 8.65-8.73 (1H, m) , 10.80 (1H,
S) , 13.80 (1H, S); IR (solid) 3359, 1720, 1624, 1597,
1561, 1538, 1500, 1475, 1435, 1410, 1358, 1329, 1283,
1261, II46, II25, 1018, 1010, 944, 827, 806, 780, 763,
703, 690, 670; MS 346.3 (M+H)+.
Example 3 03 (5-Bydraxymethyl-2ff-pyrazol-3-yl) - (2-phenyl-
quinazolin-4-yl)-arnine (III-74) : A solution of (5-
Methoxycarbonyl-2ff-pyrazol-3-yl) - (2-phenyl-quinazolin-4-
yl)-amine (III-73) {345mg, limnol) in anhydrous THF (10mL)
was treated with lithium borohydride (125mg, 5.75 mmol)
at 65°C for 5 hours. The mixture was cooled to room
temperature then combined with 2M HC1 and ethyl acetate.
Solid sodium hydrogen carbonate was added to achieve pH 8
and the resulting mixture extracted with ethyl acetate.
The extracts were dried over magnesium sulphate and
concentrated. Purification by flash chromatography (SiO2,
methanol-dichloromethane gradient) afforded IXI-74 (95
mg, 30%) as an off-white solid: mp 238-239°C; TH NMR
(DMSO) 5 4.58 (2H, d, CH2) , 5.35 (1H, s, OH), 6.94 (1H,
s), 7.50-7.60 (4H, m) , 7.85-7.90 (2H, m) , 8.48-8.54 (2H,
m) , 8.69 (1H, 1H), 10.40 (1H, s) , 12.48 (1H, s); IR
(solid) 1652, 1621, 1603, 1575, 1558, 1539, 1532, 1480,
1373, 1320, 1276, II75, 1057., 1037, 1007, 951, 865, 843,
793, 780, 7124; MS 318.2(M+H)+.

Example 304 (5-Methoxymetbyl-2H-pyrazol-3-yl) - (2-phenyl-
quinazolin-4-yl) -amine (IIX-75): rap i90-191°C; aH NMR
(DMSO) 8 3.34 (3H, s) , 4.45 (2H, s) , 7.00 (1H, s) , 7.50-
7.62 (4H, m) , 7.82-7.90 (2H, m), 8.45-8.52 (2H, m) , 8.65
(1H, br s) , 10.50 (1H, s) , 12.30 (1H, s) ; IR (solid)
3177, 1606, 1589, 1530, 1479, 1441, 1406, 1374, 1363,
1329, II52, 1099, 999, 954, 834, 813, 766,. 707, 691; MS
332.3(M+H)+.
Example 305 [5- (3-Hydroxyprop-l-yl) -2H-pyrazol-3-yl] - (2-
phenyl-quinazolin-4-yl) -amine (III-76) : A solution of (5-
benzyloxypropyl-2.H-pyrazol-3-yl) - (2-phenyl-quinazolin-4-
yl)-amine (III-78) (200mg, 0.46nmol) in toluene (4mL) and
acetonitrile (8mL) was stirred with trimethylsilyl iodide
(0.64ml, 4.6mmol) at 55°C for 3 hours to afford an amber
coloured solution. This mixture was diluted with ethyl
acetate and aqueous sodium hydrogen carbonate.. The
resulting layers were separated, the organic layer was
dried over magnesium sulphate and concentrated In vacuo.
Purification by flash chromatography (SiOa, methanol-
dichloromethane gradient) affords a yellow oil (II5mg).
Trituration with dichlorome.thane affords XII-76 as an
off-white solid dried at 75°C under vacuum (83mg, 52%): mp
164-165°C; aH NMR (DMSO) 8 1.80-1.90 (2H, m), 2.70-2.80
(2H, m) , 3.50-3.60 (2H, m), 4.59 (1H, s) , 6.80 (1H, sj,
7.50-7.60 (4H, m), 7.82-7.90 (2H, m) , 8.48-8.53 (2H, m) ,
8.63 (1H, S), 10.40 (1H, s) , 12.25 (1H, s) ; IR (solid)
1622, 1587, 1574, 1562, 1528, 1480, 1440, 1421, 136B,
1329, II73, 1052, 1030, 1006, 952, 833, 762, 734, 706,
690, 671, 665; MS 346.0(M+H)+:
Example 3 06 [5- (3-Methoxyprop-l-yl) -2H-pyrazol-3-yl] - (2-
phenyl-quinazolin-4-yl)-amine (III-77) : mp 169-170°C; '"H

NMR (DMS0-d6) 5 1.86-1.97 (2H, m) , 2.75 (2H, t) , 3.30 (3H,
S) , 3.45 (2H, t) , 6.80 (1H, s) , 7.50-7.60 (4H, m), 7J3O-
7.90 (2H, m), 8.45-8.55 (2H, m), 8.67 (1H, d), 10.30 (1H,
S), 12.25 (1H, s); IR (solid) 1620, 1591, 1572, 1532,
1476, 1425, 1408, 1373, 1326, III7, 1003, 831, 764, 714,
695; MS 360.3(M+H)+.
Example 307 [5- (3-Benzyloxyprop-l-yl) -2fi'-pyrazol-3-yl] -
(2-phenyl-quinazolin-r4-yl)-amine (III-78) : mp 177-178°C;
XH NMR (DMSO) 5 1.92-2.03 (2H, m) , 3.76-3.85 (2H, m) ,
3.52-3.62 . (2H, m), 4.51 (2H, sj, 6.82 (1H, s), 7.28-7.40
(5H, m), 7.46-7.58 (4H, m) , 7.80-7.85 (2H, m), 8.47-8.52
(2H, m) , 8.66 (1H, d) , 10.45 (1H', s) ; IR (solid) 1621,
1591, 1562, 1532, 1479, 1454, 1426, 1408, 1374, II01,
1006, 835, 766, 738, 712, 696; MS 436.3(M+H)+.
Example 308 [5- (3-Aminoprop-l-yl) -2H-pyrazol-3-yl] - (2-
phenyl-quinazolin-4-yl) -amine (III-79) : A solution of [5-
(3-tert-butoxycarbonylaminoprop-l-yl) -2H-pyrazol-3-yl] -
(2-phenyl-quinazolin-4-yl)-amine (III-80) (250mg,
0.56iranol), in dichloromethane (3mL) at 0°C was treated
with TFA (2tnL) . The mixture was warmed to room
temperature then concentrated in vacuo. The residue was
triturated and concentrated from dichloromethane (3x5mL)
and ether, then triturated with dichloromethane to
crystallize the TFA salt. The resulting solid was
collected by filtration and dissolved in a mixture of
ethanol (3mL) and water (3mL) . ? Potassium carbonate was
added in portions to achieve pH 8 then the mixture
allowed to crystallize. The product was collected by
filtration and dried at 80°C under vacuum to afford III-79
as an off-white powder (122mg, 63%) : mp 205-207°C; ^ NMR
(DMSO) 6 1.68-1.83 (2H, m) , 2.65-2.80( 4H, m) , 6.80 (1H,

s) , 7.50-7.60 (4H, m) , 7.80-7.90 (2H, m) , 8.45-8.53 (2H,.
m) , 8.65 (1H, d) , 10.45 (1H, br s); IR (solid) 1621,
1598, 1568, 1533, 1484, 1414, 1364, 1327, II69, 1030,
951, 830, 776, 764, 705, 677; MS 345.3(M+H)+.
Example 3 09 [5- (3-tert-Butoxyearbonylaminoprop-l-yl) -2H-
pyrazol-3-yl] - (2-phenyl-quinazolin-4-yl) -amine (III-80) :
mp 199-200°C; XH NMR (DMSO) 5 1.37 (9H, s) , 1.71-1.82
(2H,m), 2.67 (2H, t) , 3.00-3.II (2H, m)., 7.81 (1H, s) ,
7.-99 (1H, s) , 7.50-7.60 (4H, m) , 7.80-7.85 (2H, m) , 8.48-
8.52 (2H, m), 8.63 (1H, d), 10.40 (1H, s), 12.26 (1H, m);
IR (solid) 2953, 1687, 1622, 1594, 1573, 1535, 1481,
1441, 1419, 1364, 1327, 1281, 1252, II66, 1070, 1028,
998, 951, 848, 807, 768, 740, 728, 710,693; MS 445.3
(M+H) + .
Example 310 5-Isopropylcarbamoyl-2ff-pyrazol-3-yl) - (2-
phenyl-quinazolin-4-yl) -amine (III-81) : *H NMR (500MHz,
DMS0-d6) 8 1.20 (d, J - 6.6 Hz, 6H) , 4.13 (m, 1H), 7.42
(br. s, 1H), 7.61 (dd, J.= 7.0, 7.7 Hz, 2H), 7.66 (t, J =
7.1 Hz,. 1H), 7.71 (m, 1H), 7.99 (m, 2H) , 8.39 (m, 1H),
8.42 (d, J = 7.1 Hz, 2H), 8.74 (d, J = 8.2 Hz, 1H), II.41
(br. S, 1H) ; EI-MS 373.2 (M+H) ; HPLC-Method C, Rt 14.09
min.
Example 3II {5-Allyicarbamoyl-2ff-pyrazol-3-yl) - (2-pnenyl-
quinazolin-4-yl)-amine (III-82): ^ NMR (500MHz, DMSO-d6)
8 4.02 (m, 2H) , 5.15 (m, 1H) , 5.23 (m, 1H) , 5.94 (m, 1H) ,
7.45 (br. S, 1H), 7.60 (t, J = 6.9 Hz, 2H), 7.64 (m, 1H),
7.72 (m, 1H), 7.98 (m, 2H), 8.43 (m 2H), 8.72 (d, J = 8.2
Hz, 1H) , 8.84 (br. s, 1H), II.34 (br. s, 1H); EI-MS 371.2
(M+H); HPLC-Method C, Rt 13.67 min.

Example 312 [5- (2-Methoxyethylcarbambyl) -2H-pyrazol-3-
yl]-(2-phenyl-quinazolia-4-yl)-amine (III-83) : 1H NMR
(500MHz, DMSO-d6) 5 3.32 {s, 3H) , 3.48 (m, 4H) , 7.36 (br.
s, 1H), 7.62 (m, 2H) , 7.63 (m, 1H) , 7.71 (m, 1H) , 7.98
(m, 2H), 8.41 (dd, J .= 1.4, 7.0, 2H) , 8.70 (m, 2H), II.30
(br. S, 1H) ; EI-MS 389.2 (M+H) ; HPLC-Method C, Rt 12.37'
min.
Example 313 (5-Benzylcarbainoyl-2H-pyrazol-3-yl) - (2-
phenyl-quinazolin-4-yl)-amine (III-84) : *H NMR (500MHz,
DMS0-d6) 8 4.52 (d, J = 6.0 Hz, 2H), 7.29 (m, 1H), 7.38
(d, J = 4.2 Hz, 4H) , 7.58 (t, J = 7.5 Hz, 2H), 7.63 (m,
1H), 7.72 (m, 1H) , 7.98 (in, 2H) , 8.43 (d, J = 7.7 Hz,
2H), 8.72 (d, J ? 7.5 Hz, 1H), 9.23 (br. s, 2H), II.34
(br. s, 1H) ; EI-MS 421.2 (M+H) ; HPLC-Method C, Rt 16.76
min.
Example 314 (S-Cyclohexylcarbamoyl-iff-pyrazol-S-yl) - (2-
phenyl-quinazoliii-4-yl)-amine (III-85) : aH MMR (500MHz,
DMSO-d6) 5.1.16 (m, 1H), 1.34 (m, 4H) , 1.62 (d, J = 2.6
Hz, 1H) , 1.76 (m, 2H) , 1.85 (m, 2H), 3.79 (m, 1H), 7.43
(m, 1H) , 7.60 (t, J = 7.2 Hz, 2H) , 7.65 (t, J = 7.1 Hz,
1H), 7.71 (ddd, J = 2.2, 5.4, 8.2 Hz, 1H), 7.98 (m, 2H),
8.35 (m, 1H) , 8.43 (dd, J= 1.4, 7.2 Hz, 2H) , 8.72 (d, J
= 8.2 Hz, 1H) , II.34 (br. s, 1H) ; EI-MS 413.5 (M+H) ;
HPLC-Method C, Rt 17.18 min.
Example 315 (5-Dieth.ylcarbamoyl-2H-pyrazol-3-yl) - (2-
phenyl-quinazolin-4-yl) -amine (XIX-86) : ^H NMR (500MHz,
DMS0-d6) 5 1.18 (br. s, 3H), 1.25 (br. s, 3H), 3.49 (br.
S, 2H), 3.69 (b. s, 2H), 7.21 (s, 1H), 7.59 (t, J = 6.9
HZ, 2H), 7.62 (m,'lH), 7.70 (m, 1H), 7.96 (m, 2H), 8.39

(d, J = 7.1 Hz, 2H), 8.74 (d, J = 8.4 Hz, 1H), II.37 (br.
s, 1H) ; EI-MS 387.2 (M+H); HPLC-Method C, Rt 14.50 min.
Example 316 15- (Benzyl-methyl-carbamoyl) -2H-pyxazol-3-
yl] -(2-phenyl-quinazolin-4-yl)-amine (III-87): JH NMR
(500MHz, DMSO-d6) 6 3.33 (s, 3H) , 4.75 (s, 2H) , 7.26 (m,
1H), 7.31 (m, 1H), 7.38 (m, 4H), 7.58 (m, 2H), 7.70 (m,
1H), 7.95 (m, 3H), 8.26 (m, 1H), 8140 (d, J = 7.8 Hz,
2H) , 8.75 (m, 1H) , II.2 (br. S, 1H) ; EI-MS 435.2 .(M+H);
HPLC-Method C, Rt 16.77 min.
Example 317 (2-Phenvl-cruinazolin-4-yl) - (S-
propylcarbaaoyl-2ff-pyrazol-3-yl)-amine (III-88) : XH NMR
(500MHz, DMS0-d6) S 0.94 (t, J = 7.3 Hz, 3H) , 1.57 (m,
2H)., 3.24 (q, J = 6.5 Hz, 2H) , 7.39 (br. s, 1H) , 7.60 (t,
J =7.3 Hz, 2H), 7.64 (m, 1H), 7.71 (br. t, J = 6.5 Hz,
1H), 7.98 (m, 2H), 8.42 (d, J = 7.2 Hz, 2H), 8.61 (br. s,
1H), 8.72 (d, J = 8.5 Hz, 1H), II.34 (br. S, 1H) ; EI-MS
373.3 (M+H); HPLC-Method C, Rt 13.51 min.
Example 318 [5- (Ethyl-isopropyl-carbamoyl) -2ff-pyxazol-3-
yl] - (2-phenyl-quinazolin-4-yl) -amine (III-89) : ^ NMR
(500MHz, DMSO-d6) 8 0.92 (t, J = 7.4 Hz, 6H) , 1.52 (m,.
2H) , 1.59 (m, 1H) ', 3.79 (m, 2H) , 7.53 (br. s, 1H) , 7.57
(t, J = 7.5 Hz, 2H) , 7.65 (t, J = 7.2 Hz, 1H) , 7.71 (m,
1H), 7.99 (m, 2H), 8.23 (br. d, J = 8.8 Hz, 1H), 8.46 (d,
J - 7.5 Hz, 2H), 8.74 (d, J = 8.4 Hz, 1H), II.34 (br. s,
1H) ; EI-MS 4.01.2 (M+H); HPLC-Method C, Rt 15.51 min.
Example 319 (5-Cyclopropylcarbamoyl-2H-pyrazol-3-yl) - (2-
phenyl-quinazolin-4-yl)-amine (III-90) : ^ NMR (500MHz,
DMSO-d6) 8 0.60 (m, 2H) , 0.74 (m, 2H), 2.86 (m, 1H), 7.34
(br. s, 1H) , 7.62 (m, 3H), 7.70 (m, 1H), 7.97 (m, 2H),

8.41 (d, J = 7.9 Hz, 2H) , 8.63 (br. s, 1H), 8.72 (d, J =
7.8 Hz, 1H) , II.35. (br. S, 1H) ; EI-MS 371.2 (M+H) ; HPLC-
Method C, Rt 12.64 min.
Example' 320 (5-Isobutylcarbamoyl-2H-pyxazol-3-yl) - (2-
phenyl-quinazolin-4-yl)-amine (III-91) : 1H NMR (500MHz,
DMSO-d6) ? 0.94 (d, J = 6.7 Hz, 6H), 1.88 (m, 1H), 3.12
(t, J = 6.4 Hz, 2H), 7.45 (br. S, 1H), 7.58 (t, J = 7.2
Hz, 3H), 7.64 (t, J = 7.1 Hz, 1H) , 7.71 (m, 1H), 7.98 (m,
2H), 8.44 (dd, J = 1.3, 7.9 Hz, 2H), 8.62 (br. s, 1H),
8.72 (d, J = 8.3 Hz, 1H), II.33 (br. s, 1H); EI-MS 387.2
(M+H); HPLC-Method C, Rt 14.70 min.
Example 321 {5-[ (3S)-3-Methoxymethyl-pyrrolidine-l-
carbonyl] -2ff-pyrazol-3-yl}- (2-pnenyl-quinazoiin-4-yl) -
amine (III-93) : XH NMR (500MHz, DMS0-d6) 5 2.00 (m, 2H) ,
2.12 (m, 1H), 3.29 (s, 3H), 3.45. (t, J = 8.7 Hz, 1H),
3.57 (dd, J = 3.2, 9.3 Hz, 1H), 3.86 (m, 1H), 3.92 (m,
1H), 4.36 (m, 2H) , 7.45 (br. s, 1H), 7.59 (t, J=7.2 Hz,
2H), 7.63 (m, 1H) , 7.69 (m, 1H),.7.97 (m, 2H), 8.40 (d, J
= 7.5 Hz, 2H) , 8.74 (d, J = 7.6 Hz, 1H), II.38 (br. s,
1H) ; EI-MS 429.2 (M+H) ; HPLC-Method C, Rt 13.84 min.
Example 322 (2-Phenyl-quinazol±n-4-yl) - (5-jn-
tolylcarbamoyl-2ff-pyrazol-3-yl) -amine (III-94) : TH NMR
(500MHz, DMS0-d6) 5 2.33 (s, 3H) , 6.97 (d, J = 7.5 Hz,
1H) , 7.27 (t, J = 7.8 Hz, 1H) , 7.62 (m", 7H) , 7.72 (m,
1H) , 7.98 (m, 2H), 8.46 (dd, J = 2.0, 7.9 Hz, 2H), 8.71
(m, 1H) , 10.29 (s, 1H), II.31 (br. S, 1H); EI-MS 421.2
(M+H); HPLC-Method C, Rt 17.II min.
Example 323 (2-Phenyl-quinazolin-4-yl) -(5-p-
tolylcarbamoyl-2H-pyrazol-3-yl)-amine (III-95): 1H NMR

(500MHz, DMSO-d6) 6 2.30 (s, 3H), 7.20 (d, J =8.3 Hz,
2H) , 7.62 (m, 5H), 7.68 (d, J = 8.3 Hz, 2H) , 7.72 (m,
1H) , 7.98 (m, 2H), 8.46 (dd, J = 1.8, 7.0 Hz, 2H), 8.72
(m, 1H), 10.31 (s, 1H), II.36 (br. S, 1H); EI-MS 421.2
(M+H) ; HPLC-MetHod C, Rt 16.95 min.
Example 324 (5-Methylcarbamoyl-2H-pyrazol-3-Yl) - (2-
phenyl-quinazolin-4-yl) -amine (III-96) : 1H NMR (500MHz,
DMSO-d6) 5 2.82 (d, J = 4.6 Hz, 3H) , 7.31 (br. s, 1H) ,
7.62 (m, 3H) , 7.69 (m, 1H) , 7.97 (m, 2H) , 8.42 (d, J =
7.1 Hz, 2H), 8.59 (br. s, 1H), 8.71 (d, J = 8.0 Hz, 1H),
II.30 (br. s, 1H) ; EI-MS 345.1 (M+H); HPLC-Method C, Rt
II.02 min.
Example 325 [5- (Morpholine-4-carbonyl) -2ff-pyrazol-3-yl] -
{2-phenyl-quinazolin-4-yl)-amine (III-97) : XH MMR (500MHz,
DMSO-d6) 5 3.33 (m, 4H) , 3.83 (m 4H) , 7.34 (br. s, 1H) , .
7.53 (m, 4H) , 7.86 (m, 2H), 8.43 (m, 2H) , 8.67 (d, J =
8.6 Hz, 1H), 10.70 (s, 1H) , 13.56 (s, 1H) ; EI-MS 401.2
(M+H) ; HPLC-Method A, Rt 2.68 min.
Example 326 [5- (1 -Methylpiperazine-4-carbonyl) -2H-
pyrazol-3-yl] - (2-phenyl-quinazolin-4-yl) -amine (III-98) :
XH NMR (500MHz, DMSO-d6) 8 2.25 (s, 3H) , 2.43 (m, 4H) ,
3.87 (m 4H), 7.33 (br. s, 1H) , 7.53 (m, 4H) , 7.87 (m,
2H) , 8.45 (m, 2H) , 8.67 (d, J. = 7.6 Hz, 1H) , 10.70 (s,
1H) , 13.30 (s, 1H) ; EI-MS 414.2 (M+H); HPLC-Method A, Rt
2.38 min.
Example 327 [5- (2-Hydroxyethylcarbamoyl-2fl-pyrazol-3-yl] -
(2-phenyl-quiaazolin-4-yl)-amine (III-99) : ^ NMR (500MHz,
DMSO-d6) 8 3.36 (m, 2H), 3.52 (m, 2H), 4.79 (m, 1H), 7.50
(m, 5H), 7.83 (m, 2H), 8.50 (m, 4H) , 10.52 (br. s, 1H),

13.25 (s, 1H) ; EI-MS 375.1 (M+H) ; HPLC-Method A, Rt 2.51
min.
Example 328 (5-Carbamoyl-2H-pyrazol-3-yl) - (2-phenyl-
guinazolin-4-yl) -amine (III-100) : To a solution of 5-(2-
phenyl-quinazolin-4-ylamino) -lH-pyrazole-3-carboxylic
acid 2,5-dioxo-pyrrolidin-l-yl ester (270 mg, 0.63 mmol)
in DMF (20 ml) was added a solution of ammonia in 1,4-
dioxane (0.5 M, 10 ml). The resulting mixture was
stirred at room temperature for 24 h. After
concentration of the solvents, the residue was added to
water (20 ml) . The resulting precipitate was collected
to afford III-100 (168 mg, 80%)as a yellow solid. 1H NMR
(500MHz, DMSO-d6) ? 7.77-7.51 (m, 6H) , 7.86 (br s, 2H) ,
8.II (m, 1H) , 8.50 (m, 2H) , 8.63 (m, 1H), 10.52 (s, 1H) ,
II.25 (s, 1H) ; EI-MS 331.1 (M+H); HPLC-Method A, Rt 2.52'
min.
Example 329 (4-Bromo-2H-pyrazol-3-yl) -(2-phenyl-
quinazolin-4-yl)-amine (III-101) : Prepared according to
Method A to afford a yellow solid, mp 189°C; 1H NMR (DMSO-
d6) 8 7.44-7.46 (3H, m), 7.58 (1H, m) , 7.87 (2H, d) , 8.15
(1H, s) , 8.31-8.34 (2H, m) , 8.49 (1H, d) , 10.08 (1H, s) ,
13.13 (1H, S); IR (solid) 3286, 2969, 1738, 1632; MS
366.2/368.2(M+H)+.
Example 330 (4-Bromo-5-methyl-2H-pyrazol-3-yl) - (2-phenyl-
quinazolin-4-yl)-amine (III-102): mp 183-185°C; 1H NMR
(DMSO) ? 2.33 (3H, br s), 7.44-7.46 (3H, m), 7.57 (1H,
m) , 7.84-7.87 (2H, m), 8.31-8.34 (2H, m), 8.48 (1H, d) ,
10.05 (1H, s), 12.91 (1H, br s) ; IR (solid) 3362, -3065,
2831, 1619, 1578; MS 380-2/382.2(M+H)+.

Example 331 (4-Cyano-2H-pyrazol-3-yl) -(2-phenyl-
quiaazolin-4-yl)-amine (III-103) : rap >250°C; 1H NMR (DMSO)
? 7.47-7.49 (3H, m), 7.64 (1H, m), 7.91 (2H, m) , 8.40-
8.43 (2H, m), 8.53 (1H, d), 8.71 (1H, d), 10.61 (1H, s),
13.60 (1H, s); IR (solid) 3277, 3069, 2855, 2231, 1625;
MS 313.2(M+H)+.
Example 332 (5-Methyl-2H-pyrazol-3-yl) - (2-morpholin-4-yl-
quinazolin-4-yl) -amine {III-104): mp 223-224°C; 1H NMR
(DMSO) ? 2.26(3H, s), 3.65(4H, m), 3.75(4H, m), 6.44(1H,
s) , 7.12(1H, d) , 7.33(1H, d) , 7.56(1H, t) , 8.37(1H, d) ,
10.0K1H, s), 12.13(1H, br s) ; IR (solid) 1621, 1578,
1537, 1475, 1434, 1385; MS 3II.0 (M+H)+.
• Example 333 (5-Methyl-2H-pyrazol-3-yl) - (2-piperazin-l-yl-
quinazolin-4-yl) -amine (III-105): mp 179-181°C; *H NMR
(DMSO) 5 2.26(3H, s), 2.74 (4H, br s) , 3.71(4H, br s),
6.43(1H, s), 7.08(lH, t), 7.3O(1H, d), 7.53(1H, t),
8.34 (1H, d) , 9.50 (1H, s) , 12.08 (1H, br s) ,- IR (solid)
2853, 1619, 1603, 1566, 1549, 1539; MS 310.0 (M+H)+
Example 334 [2- (4-Methylpiperidin-l-yl) -quin.azolin-4-yl] -
(5-methyl-2H-pyrazol-3-yl)-amine (III-106) : mp 148-150°C;
^ NMR (DMSO) 8 1.06(3H, d), 1.03(2H, m), 1.51-1.70(3H,
m) , 2.26(3H, s), 2.86(2H, m), 4.73(2H,d), 6.44(1H, s),
7.06(lH, d), 7.29(1H, d), 7.52(1H, t), 8.32(1H, d),
9.92(1H, s), 12.09(lH, br s); IR (solid) 2917, 2840,
1629, 1593, 1562, 1546, 1486; MS 323.0 (M+H)+.
Example 335 12- (4-Methylpiperazin-l-yl) -quinazolin-4-yl] -
(5-methyl-2H-pyrazol-3-yl)-amine (III-107): mp 105-107°C;
1H NMR (DMSO) ? 2.21(3H, s), 2.26(3H, s), 2.34(4H, m),
3.75(4H, m), 6.45(1H, s), 7.09(lH, t), 7.31(1H, d) ,

7.54(1H, t), 8.34(1H, d), 9.96(1H, s), 12.12(1H, br s);
IR (solid) 2934, 2844, 2804, 1620, 1593, 1572, 15360,
1476; MS 324.0 (M+H)+.
Example 33 6 (5-Methyl-2H-pyrazol-3-yl) - (2-piperidin-l-yl-
quinazolin-4-yl)-amine (III-108) : rap 294°C; 1H NMR (DMSO)
S 1.45-1.58 (4H, m), 1.63 (2H, m), 2.26 (4H, m) , 6.45 (1H, br s) , 7.06 (1H, t) , 7.29 (1H, d) ,
7.52 (1H, t) , 8.33 (1H, d) , 9.92 (1H, s) , 12.II (1H, br
s); IR (solid) 2929, 2847, 1632, 1591, 1500, 1482, 1437,
1382; MS 309.3 (M+H)+.
Example 337 (2-Azepan-l-yl) -quinazolin-4-yl] - (5-metbyl-
2H-pyrazol-3-yl)-amine (III-109) : mp 269°C; 1H NMR (DMSO)
? 1.50 (4H, br s), 1.76 (4H, br s), 2.25 (3H, s), 3.78
(4H, t) , 6.55 (1H, br s) , 7.03 (1H, t) , 7.28 (1H, d) ,
7.50 (1H, t), 8.33 (1H, d), 9.92 (1H, s) , 12.09 (1H, br
s); IR (solid) 3427, 2963, 2927, 2909, 2872, 2850, 1623,
1595, 1586, 1568., 1504, I486, 1468, 1386, 1427; MS 323.3
(M+H) + .
Example 33 8 [2-(4-(2-Hydroxyethylpiperidin-l-yl)-
quinazolin-4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine {XIX-
II0): mp 175°C; XH NMR (DMSO) 5 1.08 (2H, m), 1.38 (2H,
m) , 1.57-1.83 (3H, m), 2.26 (3H, s), 2.85 (2H, t), 3.47
(2H, m) , 4.38 (1H, t), 4.75 (2H, d) , 6.45 (1H, br s),
7.06 (1H, t), 7.29 (1H, d), 7.52 (1H, t), 8.32 (1H, d),
9.93 (1H, s), 12.12 (1H, br s); IR (solid) 3365, 3073,.
2972, 2868, 1622, 1604, 1586, 1568, 1486, 1463, 1440,
1394; MS 353.2 (M+H) + .
Example 339 (5-Cyclopropyl-2H-pyrazol-3-yl)-[2-(4-
methylpiperidin-1-yl) -quinazolin-4-yl] -amine (III-lll) :

To a solution of (5-cyclopropyl-lH-pyrazol-3-yl) - (2-
chloro-quinazolin-4-yl) -amine (II8 ing, 0.41 mmol) in
tert-butanol (3.0 mL) was added 4-methylpiperidine (0.49
mL, 4.1 mmol) and the reaction mixture heated at reflux
overnight. The reaction mixture was concentrated In
vacuo and the residue dissolved in a mixture EtOH: water
(1:3,'4 mL) . Potassium carbonate (57mg, 0.41 mmol) was
added and the mixture stirred at room temperature for 2
hours. The resulting suspension was filtered, washed
with water (x2) / and rinsed with Et2O (x2) to afford III-
III as a white solid (123mg, 85%): mp 190°C; XH NMR (DMSO)
5 0.66 (2H, S) , 0.93. (5H, tes), 1.07 (2H, d), 1.66 (3H,
s) , 1.91 (1H, s), 2.85 (2H, t) , 4.72 (2H, d) , 6.33 (1H,
s) , 7.06 (1H, t), 7.29 (1H, d), 7.52 (1H, t) , 8.31 (1H,
d), 9.95 (1H, s), 12.18 (1H, br s); IR (solid) 2925, '
2852, 1622, 1590, 1581, 1558, 1494, 1481, 1453, 1435,
1394; MS 349.2 (M+H)+.
Example 340 [2- (l,4-D±oxa-8-aza-sp±ro [4,5] dec-8-yl) -
quinazolin-4-yl]- (5-methyl-2J5r-pyrazol-3-yl) -amine (III-
II2): mp 191°C; XH NMR (DMSO) 8 1.65 (4H, S.) , 2.26 (3H,
s), 3.90 (4H, s), 3.93 (4H, s) , 6.43 (1H, br s), 7.09
(1H, t) , 7.32 (1H, d) , 7.54 (1H, t) , 8.35 (1H, d.) , 9.99
(1H, br s), 12.13 (1H, br s); IR (solid) 3069, 2964,
2927, 2868, 1618, 1581, 1568, 1540, 1495, 1481, 1435,
1390; MS 367.3 (M+H)+.
Example 341 [2- (4-Cyclopentylamino-piperidin-l-yl) -
guinazolin-4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (III-
II3): mp 191°C; 1H NMR (DMSO) ? 1.33 (2H, d) , 1.65 (4H,
s), 1.87 (2H, d), 2.20 (1H, s), 2.26 (3H, s), 2.49 (2H,
s), 3.00 (2H, t), 3.36 (2H, s) , 4.61 (2H, d), 6.45 (1H,
br s), 7.07 (1H, s), 7.31 (1H, d), 7.52 (1H, s), 8.33

{1H, d) , 9.94 (1H, br s), 12.12 (1H, br s) ; IR (solid)
3371, 2943, 1622, 1600, 1581, 1545, 1509, 1463, 1440,
1390; MS 378.2 (M+H)+.
Example 342 12- (4-Hydroxypiperidin-l-yl) -guinazolin-4-
yl]-(5-methyl-2jr-pyrazol-3-yl)-amine (III-II4): mp 123°C;
XH SMR (DMSO) 8 1.34 (2H, d), 1.80 (2H, d), 2.26 (3H, s) ,
3.24 (2H, t), 3.72 (1H, br s), 4.39 (2H, d), 4.70 (1H,
d), 6.44 (1H, br s), 7.07 (1H, t), 7.30 (1H, d),7.53
(1H, t), 8.33 (1H, d), 9.94 (1H, br s), 12-II (1H, br s>;
IR (solid) 3265, 3151, 2927, 2863, 1622, 1600, 1572,
1540, 1504, 1476, 1440, 1390, 1349, 1066, 1098; MS 325.3
(M+H)+.
Example. 343 (5-Cyclopropyl-2i?-pyrazol-3-yl) - [2- (4-
hydroxy-4-phenylpiperidia-l-yl) -guinazolin-4-yl] -amine
(III-II5) : nrp 131°C; '"H NMR (DMSO) 5 0.64 (2H, q) , 0.93
{2H, q), 1.68 (2H, d), 1.83-1.97 (3H, m) , 3.20-3.45 (2H,
m) , 4.69 (2H, d), 5.II (1H, s) , 6.37 (1H, br s), 7.08
(1H, t)', 7.20 (1H, t), 7.31 (3H, t) , 7.49 (2H, d), 7.53
(1H, t), 8.33 (1H, d) , 9.98 (1H, br s), 12-18 (1H, br s);
IR (solid) 3362, 2952, 2934, 29II, 2870, 2825, 1618,
1584, 1570, 1559, 1536, 1481, 1459, 1431, 1372, 1336,
1213, 994; MS 427.6. (M+H)+.
Exaarple 344 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (1,3-
dihydro-isoindol-2-yl)-quinazolin-4-yl]-amine (III-II6) :
Prepared according to Method E-I to afford an off-white
solid, mp 237°C; hi NMR (DMSO-d6) 5 0.79 (2H, s), 1.00
(2H, d) , 1.99 (1H, m), 4.92 (4H, d), 6.72 (1H, br s),
7.13 (1H, t), 7.33 (2H, s), 7,30-7.48 (3H, m), 7.58 (1H,
t) , 8.40 (1H, d) , 10.12 (1H, s), 12.17 (1H, s); IR
(solid) 3449, 3318, 2850, 1623, 1595, 1577, 1541, 1509,

1482, 1432, 1391, 1359, II41, 1027, 877, 814; MS 369.4
(M+H)+.
Example 345 (2-Azepan-l-yl)-quinazolin-4-yl]-(5-
cyclopropyl-2H-pyrazol-3-yl) -amine (III-H7) : mp 199-
200°C; 1H NMR (DMSO-d6) ? 0.60-0.70 (2H, n), 0.90-1.00
(2H, m) , 1.45-1.57 (4H, m) , 1.70-1.85 (4H, m), 1.88-1.97
(1H, m), 3.75-3.87 (4H, m), 6.42 (1H, s), 7.02 (1H, t),
7.27 (1H, d) , 7.49 (1H, t), 8.29 (1H, d) , 9.91 (1H, s) ,
12.19 (1H, br s) ; IR (solid) 2929, 1624, 1595, 1581, .
1563, 1542, 1498, 1482, 1440, 1426, 1397, 1356, 1305,
1000, 825, 754; MS 349.2 (M+H)+.
Example 346 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (3,4-
dihydro-lH-iBoquinolin-2-yl) -quinazolin-4-yl] -amine (III-
II8): mp 182-184°C; 1H NMR (DMSO) ? 0.75 (2H, d) , 1.02
(2H, d) , 1.96 (1H, m) , 2.89 (2H, m) , 4.05 (2H, m) , 4.94
(2H, s) , 6.46 (1H, s), 7.10 (1H, t), 7.21 (4H, d) , 7.37
(1H, d) , 7.55 (1H, d) , 8.36 (1H, d), 10.05 (1H, s) , 12.23
(1H, br s) ; IR (solid) 1621, 1581, 1560, 1537, 1479,
1456, 1426, 1396, 1374, 1341, 1222; MS 383.3 (M+H)+.
Example 347 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (2,3-
dibydro-indol-1-yl)-quinazolin-4-yl]-amine (III-II9) : mp
150-153°C; 1H NMR (DMSO) ? 0.74 (2H, d) , 0.98 (2H, d) ,
1.96 {1H, m) , 3.15 (2H, t) , 4.25 (2H, t) , 6.45 (1H, br
s) , 6.88 (1H, t), 7.09 (1H, t), 7.20 (2H, m), 7.53 (1H,
d) , 7.65 (1H, t), 8.43 (2H, br s), 10.09 (1H, s) , 12.28
(1H, br s) ; IR (solid) 1621, 1588, 1577, 1564, 1537,
1487, 1455, 1425, 1386, 1259; MS 369.3 (M+H)+.
Example 348 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2-(4-
hydroxymethylpiperidin-1-yl) -guinazolin-4-yl] -amine (III-

120): mp 142°C; 1H MMR (DMSO) ? 0.67 (2H, d) , 0.96 (2H,
d) , 1.10 (2H, q) , 1.55-1.70 (3H, m) , 1.91 (1H, m) , 2.85
(2H, t), 3.28 (2H, s), 4.48 (1H, s) , 4.76 (2H, d) , 6.34
(1H, s), 7.06 (1H, t), 7.30 (1H, d) , 7.52 (1H, t), 8.31
(1H, d), 9.96 (1H, s), 12.19 (1H, s); IR (solid) 3363,
3000, 2927, 2854, 1618, 1604, 1573, 1536, 1509, 1477,
1436, 1395, 1354, 1314, 1241, II86, 1091, 995, 941, 823;
MS 365.8 (M+H)+.
Example 349 (5-Cyclopropyl-2H-pyrazol-3-yl) - [2- (3,4-
dihydro-2H-quinolin-l-yl) -quinazolin-4-yl] -amine (III-
121): mp 137-145°C; 1H NMR (DMSO-d6) ? 0.55 (2H, d) , 0.88
(2H, d), 1.78 (1H, m) , 1.92 (2H, t) , 2.75 (2H, t), 4.04
(2H, t) , 6.20 (1H, br s) , 6.97 (1H, t) , 7.14 (1H, m) ,
7.19 (1H, t), 7.42 (1H, d), 7.61 (1H, t), 7.67 (1H, d),
8.43 (1H, d), 10.04 (1H, s), 12.21 (1H, br s); IR (solid)
1622, 1572, 1539, 1493, 1454, 1420, 1373, 1249; MS 383.3
(M+H)+.
Example 350 (5-Methoxycarbonyl-2H-pyrazol-3-yl)-[2-
(piperidine-1-yl) -quinazolin-4-yl] -amine (III-122) : *Tl NMR
(500MHz, CDC13) 81.7-1.8(6H, m) , 8 3.8 (4H, m), 8 3.9 (3H,
s), 5 5.5 (1H, s), 8 7.15 (1H, t), 8 7.4 (1H, d), 8 7.6
(1H, t) , 8 8.0 (1H, d) . HPLC-Method B, (starting with 95%
H20) Rt 7.4 min; MS (ES+) 353.24 (M+H) .
Example 351 [5-(Piperidine-1-carbonyl)-2ff-pyrazol-3-yl]-
[2- (piperidine-1-yl) -quinazolin-4-yl] -amine (III-123) :
HPLC-Method B, (starting with 95% H20:0.1% TFA) Rt 8.0
min; MS (ES+) 406.30, (ES-) 404.30.
Example 352 (5-Hydroxymetbyl-2H-pyrazol-3-yl) -[2-
(piperidin-1-yl)-quinazolin-4-yl]-amine (III-124): To a

solution of III-122 (10.0 mg, 0.028 mmol) in THF (6 mL)
at ambient temperature was slowly added a 1M solution of
LiAlH4 in THF (0.05 mL, 0.05 mmol). After 15 minutes the
solution was quenched with water and IN HCl. The product
was extracted from the aqueous layer with EtOAc. The
organic layer was dried over MgSO4, filtered, and
concentrated in vacuo. The residue was purified by
preparatory HPLC to afford III-124 (4.0 mg, 44%). HPLC-
Method B, (starting with 95% H2O:0.1% TFA) Rt 6.1 min; MS
(ES+) 325.13 (M+H), (ES-) 323.13 (M-H).
Example 353 (5-Carbamoyl-2H-pyrazol-3-yl) - [2- (piperidin-
1-yl)-quinazolin-4-yl]-amine (III-125) : A solution of
III-122 (1.5 g, 4.3 mmol) in 2.0 M NH3/MeOH (100 mL) was
heated at II0°C for 2 days. The dark brown reaction
mixture was concentrated in vacuo to afford a viscous oil
which was purified by column chromatography to yield 0.7
g (50%) of III-125. 1H NMR (500MHz, CD3OD-d3) ?1.6
(4H, m); 81.7 (2H,m), ? 3.3 (1H, s) , ? 3.8 (4H, m) , ? 5.5
(1H, S), ? 7.15 (1H, t), ? 7.45 (1H, d), ? 7.55 (1H, t) , ?
8.0 (1H, d) ; HPLC-Method B, (starting with 95% H2O:0.1%
TFA) Rt 5.9 min; MS (ES+) 3.38.13, (ES-) 336.15.
Example 354 (5-Carbamoyl-2H'-pyrazol-3-yl) - [2- (4-
methylpiperidin-1-yl)-guinazolin-4-yl]-amine (III-126) :
HPLC-Method B, (starting with 95% H2O:0.1% TFA) Rt 6.4
min; MS (ES+) 352.19, (ES-) 350.20.
Example 355 (5,7-Difluoro-lH-indazol-3-yl) - (2-phenyl-
5,6,7,8-tetrahydroquinazolin-4-yl)-amine (III-127) : XH NMR
(500 MHz, DMSO-de) 813.7 (s, 1H), 10.3 (s, br, 1H) , 7.90
(d, 2H), 7.52 (t, 1H) , 7.45 (m, 3H),.7.26 (d, 1H), 2.99

(m, 2H) , 2.75 (m; 2H) , 1.95 (br, 4H) ppm; MS (ES+) 378.24
(M+H); .(ES-) 376.23 (M-H) ; HPLC-Method A, Rt 3.04 min.
Example 356 (2-Phenyl-5,6,7,8-tetrahydroquinazolin-4-yl) -
(5-trifluoramethyl-lff-indazol-3-yl)-amine (III-128) : lH
NMR (500 MHz, DMSO-d6) 813.4 (e, 1H) , 10.2 (s, br, 1H) ,
8.13 (s, 1H), 7.86 (d, 2H), 7.78 (d, 1H), 7.69 (d, 1H) ,
7.50 (t, 1H), 7.35 (dd, 2H) 7 2.89 (m, 2H) , 2.72 (m, 2H) ,
1.90 (s, br, 4H) ppm.; MS (ES+) 410.24 (M+H); (ES-) 408.23
(M-H); HPLC-Method A, Rt 3.19 nin.
Example 357 (7 - Fluoro - Iff- indazol - 3 -yl) - (2 -phenyl -
quinazolin-4-yl)-amine (III-129) : XH NMR (500 MHz, DMSO-
d6) 813.6 (s, 1H) , II.1 (s, br, 1H) , 8.65 (d, 1H) , 8.03
(d, 2H) , 7.95 (s, 2H) , 7.67 (m, 1H), 7.45 (m, 2H) , 7.33
(t, 2H) , 7.22 (dd, 1H) , 6.99 (td, 1H) ppm. MS (ES+) : m/e=
.356.20 (M+H); HPLC-Method A Rt 3.00 min.
Example 358 (5-Fluoro-lff-indazol-3-yl) - (2-phenyl-
quinazolin-4-yl) -amine (XIX-130): ^ NMR (500 MHz, DMSO-
d6) 813.2 (s, 1H), II.3 (s, br, 1H) , 8.67 (d, 1H), 8.04
(d, 2H), 7.96 (s, 2H), 7.70 (m, 1H) , 7.58 (dd, 1H), 7.43
(m, 4H), 7.28 (td, 1H) ppm. MS (ES+) 356.20 (M+H); HPLC-
Method A, Rt 3.00 min.
Example 359 (5,7-Difluoro-lff-indazol-3-yl) - (2-phenyl-
quinazolin-4-yl) -amine (III-131): 1H NMR (500 MHz, DMSO-
d6) 813.7 (s, 1H), 8.65 (d, 1H), 8.04 (d, 2H) , 7.95 (s,
2H), 7.68 (m, 1H) , 7.45 (m, 1H) , 7.35 (m, 4H) ppm. MS
(ES+) : m/e= 374.17 (M+H); HPLC-Method A, Rt 3.07 min.
Example 360 (Iff-Indazol-3-yl) - [2- (3-trifluoromethyl-
phenyl)-quinazolin-4-yl] -amine (III-132) : ^ NMR (500MHz,

DMSO-d6) ? 7.06 (t, 1H), 7.42 (t, 1H), 7.59 (d, 1H) , 7.63
(t, 1H), 7.66 {d, 1H) , 7.71 (m, 1H) , 7.80 (d, 1H) , 7.98
(m, 2H), 8.33 (s, 1H) , 8.46 (d, 1H) , 8.71 (d, 1H) , II.04
(br. S, 1H), 12.97 (s, 1H); El-MS 406.1 (M+l) ; HPLC-
Method A, Rt 3.15 min.
Example 361 (2-Phenyl-quinazolin-4-yl) - (lH-pyrazolo [4,3-
b]pyridin-3-yl)-amine (XII-133): 1H NMR (500 MHz, DMSO-d6)
?13.3 (s, br, 1H) , II.4 (s, br, 1H) , 8.78 (d, 1H) , 8.58
(dd, 1H) , 8.24 (d, 1H), 8.10 (m, 2H), 7.95 (d, 2H) , 7.86
(t, 1H) , 7.56 (m, 2H) , 7.44 (t, 2H) ppm. MS (ES+) 339.II
(M+H) ; HPLC-Method A, Rt 2.63 min.
Example 362 [5- (3-Methoxy-phenyl) -6-oxo-5, 6-dihydro-1H-
pyrazolo [4,3-c] pyridazin-3-yl] - (2-phenyl-quinazolin-4-
yl)-amine (III-134) : 1H NMR (500 MHz, MeOH-d4) ?8.65 (d,
1H), 8.17 (m, 3H), 8.10 (d, 1H), 7.90 (t, 1H) , 7.75 (t,
1H), 7.58 (m, 2H), 7.25 (t, 1H), 6.95 (m, 2H) , 6.85 (d,
1H), 6.80 (s, 1H), 3.64 (s, 3H) ppm. MS (ES+) : m/e=
462.2(M+H).
Example 363 (6-Oxo-5-phenyl-5,6-dihydro-lH-pyrazolo[4,3-
c]pyridazin-3-yl) - (2-phenyl-quinazolin-4-yl) -amine (III-
135): 1H NMR (500 MHz, MeOH-d4) ?8.61 (d, 1H) , 8.13 (m,
3H) , 8.05 (d, 1H), 7.85 (t, 1H), 7.70 (t, 1H) , 7.58 (m,
2H), 7.32 (m, 5H), 6.79 (s, 1H) ppm. MS (ES+) : m/e«
432.2(M+H).
Example 3 64 [5- (4-Methoxy-phenyl) -6-oxo-5, 6-dih.ydro-lH-
pyrazolo [4,3-e]pyridazin-3-yl] - (2-pnenyl-quinazolin-4-
yl)-amine (III-136): MS (ES+) 462.2(M+H).

Example 365 [5- (2,4-Dichloro-phenyl) -6-oxo-5, 6-dihydro-
lH-pyrazolo[4,3-e]pyridazin-3-yl] - (2-phenyl-quinazolin-4-
yl)-amine (III-137): 1H NMR (500 MHz, MeOH-d4) ?8.63 (d,
1H) , 8.17 (m, 4H), 7.89 (t, 1H), 7.73 (t, 1H), 7.61 (t,
2H), 7.57 (d, 1H), 7.32 (m, 1H) , 7.21 (d, 1H) , 6.84 (s,
1H) ppm. MS (ES+) : m/e= 500.1(M+H).
Exaaple 366 [6-0X0-5- (3-trifluoromethyl-phenyl) -5, 6-
dihydro-lH-pyrazolo[4,3-c]pyridazin-3-yl] - (2-phenyl-
quiaazolin-4-yl) -amine (III-138) : XH NMR (500 MHz, MeOH-
d4) 58.55 (d, 1H), 8.19 (d, 2H) , 7.92 (m, 2H), 7.65 (m,
3H), 7.45 (t, 2H), 7.25 (t, 1H), 7.13 (t, 1H), 7.05 (t,
1H), 6.75 (s, 1H) ppm. MS (ES+) : m/e«= 500.2 (M+H) .
Example 367 [6-Oxo-5- (4-Pbenoxy-pheayl) -5, 6-dihydro-lH-
pyrazolo [4, 3-c]pyridazin-3-yl] - (2-phenyl-qu.iaazolln.-4-
yl)-amine (III-139): MS (ES+) 524.3(M+H). •
Example 368 £5- (4-Chloro-phenyl) -6-oxo-5, 6-dihydro-lH-
pyrazolo [4,3-eJpyridazi»-3-yl3 - (2-phenyl-guinazolin-4-
yl)-amiae (III-140): MS (ES+) 466.2(M+H).
Example 369 (2-imidazol-l-yl-quinazolin-4-yl) - (1H-
indazol-3-yl)-amine (III-141) .- XH HMR (500MHz, DMSO-d6) 8
7.10 (t, 1H), 7-44 (t, 1H), 7.50 (i>r. s, 1H) , 7.60 (d,
1H), 7.72 (tn, 2H), 7.77 (m, 1H) , 7.88 (d, 1H) , 7.98 1H), 8.73 (d, 1H), 8.96 (s, 1H), II-23 (s, 1H) , 13.06 (s,
1H) ; El-MS 328.1 (M+l) ; HPLC-Method A, Rt 2.93 min.
T^a^le 370 (lH-Indazol-3-yl) - [2- (2-xnfitbyl-imidazol-l-yl-
qainazolin-4-yl]-amine (III-142) : XH NMR (500MHz, DMSO-d6)
8 2.48 (S, 3H), 7.10 (t, 1H), 7-43 (t, 1H), 7.57 (d, 1H),
7.60 (d, 1H), 7.67 (d, 1H), 7.76 (td, 1H), 7.86 (d, 1H),

7.91 (d, 1H) , 8.01 (td, 1H) , 8.72 (d, 1H) , II.15 (s, 1H) ,
13.10 (s, 1H) ; El-MS 342.1 (M+l) ; HPLC-Method A, Rt 3.06
min.
Example 371 (lff-Indazol-3-yl) - (2-piperidin-l-yl-
quinazolin-4-yl)-amine- (III-143) : *H NMR (SOOMHz, DMSO-d6)
8 1.48 (m, 6H) , 3.60 (mf 4H) , 7.II (t, 1H), 7.52 (t, 1H) ,
7.55 (d, 1H), 7.64 (d, 1H) , 7.69 (d, 1H), 7.75 (d, 1H) ,
7.90 (t, 1H) , 8.58 (d, 1H), II.82 (br. s, 1H) , 13.25 (s,
1H) ; EI-MS 345.1 (M+l); HPLC-Method A, Rt 3.03 min.
Example 372 (lH-Indazol-3-yl) - [2- (oetah.ydro-quinolin-1-
yl)-quinazolin-4-yl]-amine (III-144): XH NMR (500MH2,
DMSO-d6) 8 0.6-1.9 (m, 13 H) , 3.15 (a, 1H) , 3.25 (m, 1H),
4.0 (m, 1H), 7.10 (t, 0.5H), 7.12 (t, 0.5H), 7.55 (m,
2H), 7.66 (d, 0.5 H), 7.69 (d, 0.5 H), 7.77 (d, 1H) , 7.91
(t, 1H), 8.55 (d, 0.5 H) , 8.59 (d, 0.5 H), II.46 (s, 0.5
H) , II.54 (s, 0.5 H)# II.78 (s, 0.5 H) , II.84 (s, 0.5 H) ,
13.10 (S, 0.5 H), 13.12 (s, 0.5 H); EI-MS 399.3 (M+l); ?
HPLC-Method A, Rt 3.37 min.
Example 373 (lff-Indazol-3-yl) - [2- (2# 6-dimethyl-morpholin-
. 4-yl)-quinazolia-4-yl]-amine (III-145)-. XS. NMR (500MHz,
DMSO-d6) 8 1.0 (m, 6H), 4.0 (m, 6H), 7.12 (t, 1H) , 7.41 .
(td, 1H), 7.56 (t, 1H), 7.58 (d, 1H), 7.68 (dd, 1H), 7.77
(t, 1H) , 7.93 (t, 1H) , 8.60 (d, 1H) , II.69 (s, 1H) , 13.16
(s, 1H) ; EI-MS 375.3 (M+l); HPLC-Method A, Rt 2.93 min.
Example 374 (5-Methyl-2fl'-pyrazol-3-yl) - (2-phenyl-
pyrimidin-4-yl)-amiixe (IV-1)-. mp 245-246°C; XH NMR (DMSO)
8 2.26 (3H, s), 6.32 (1H, br s), 7.07 (1H, br s), 7.48-
7.54 (3H, m) , 8.33-8.39 (3H, m), 9.87 (1H, s), 12.03 (1H,

s); IR (solid) 1628, 1589, 1579, 1522, 1479, 1441, 1393,
1336; MS 252.2 (M+H)+.
Example 375 [6- (4-Acetamidophenylsulfanyl)-2-phenyl-
pyrimidin-4-yl] - {5-methyl-2H-pyrazol-3-yl} -amine (IV-3) :
A suspension of Fenclorim (4, 6-dichloro-2-
phenylpyrinddine) (0. lg, 0.44 mmol) , 3 -amino-5-
methylpyrazole (0.045 g, 0.47 mmol), N, N-
diisopropylethylamine (0.08 ml, 0.47 nmol) and sodium
iodide (0.067 g, 0.44 mmol) in n-butanol (5 ml) were
heated at II7 oC for 18 hours. The solvent was removed in
vacuo and the crude product purified by flash
chromatography (silica gel, 3:2 Petrol:EtOAc) to afford
0.037 g (29 % yield) of (6-Chloro-2-phenyl-pyrimidin-4-
yl) - (5-methyl-2H-pyrazol—3-yl) -amine as a off-white
solid. A suspension of the above pyrimidine (0.037 g,
0.13 mmol) and thioacetamidothiophenol (0.108 g, 0.64
mmol) in tert-butanol was heated at 85 °C under nitrogen
for 2 days. The reaction mixture was cooled to room
temperature and the solvent removed in vacuo. The
concentrate was dissolved in EtOAc, and washed with NaHCO3
(sat, aq.) . The organic layer is concentrated in vacuo,
and the crude product by preperative HPLC. The residual
disulfide that still remained in the mixture after HPLC
may be removed by precipitation from EtOAc and
filtration. The mother liquor was concentrated to afford
IV-3 (7mg, 13 % yield) as an off-white solid: mp 235-
236°C; *H NMR (DMSO) 5 2-10 (3H, s) , 2.21 (3H, s) , 6.33
(1H, br s), 7.50 (3H, m), 7.7-7.59 (2H, m), 7.76-7.78
(2H, m), 8.25 (2H, m) , 9.72, 10.26 and II.93 (3 H, 3 x br
s); IR (solid) 1669. 1585, 1551, 1492, 1392, 1372, 1312,
1289, 1259, II74, II02, 1089, 1027, 1015, 984; MS 417.3
(M+H) + .

Example 376 [2- (4-Methylpiperidin-l-yl) -pyrimidin-4-yl] -
(5-methyl-2H-pyrazol-3-yl)-amine (IV-4) : mp 215-216°C; 1H
NMR (CD3OD) ? 0.96 (3H, d) , 1.16 (2H, m), 1.66 (3H,- m) ,
2.27 (3H, s), 2.86 (2H, t) , 4.58 (2H, m), 4.78 (2H,
exch.protons) , 6.13 (2H, m) , 7.83 (1H, d) ; IR (solid)
1593, 1550, 1489, 1436, 1331, 1246, 1231; MS 273.1 (M+H)+.
Example 377 [2- (4-Methylpiperidin-l-yl) -5-nitropyrimidin-
4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (IV-5) : mp 185-
187°C; 1H NMR (DMSO) 5 0.93 (3H, d) , 1.06-1.18 (2H, m) ,
1.68-1.80 (3H, m) , 2.26 (3H, s), 3.01-3.12 (2H, m), 4.63
(1H, d), 4.80 (1H, d), 6.39 (1H, s) , 9.00 (1H, s), 10.41
(1H, s), 12.36 (1H, s); IR (solid) 1589, 1517, 1479,
1446, 1346, 1317, 1246, 1222, 1055; MS 318.2 (M+H)+.
Example 378 [5-Amino-2- (4-Methylpiperidin-l-yl) -
pyrimidin-4-yl] - (5-methyl-2H'-pyrazol-3-yl) -amine (IV-6) :
To a solution of IV-5 (48 mg, 0.151 mmol) in ethanol (2.0
mli) was added tin dichloride dihydrate (171 mg, 0.756
mmol) and the resulting mixture heated at reflux for 3
hours. The reaction was cooled to room temperature and
poured onto a mixture of 1M NaOH: dichloromethanerpropanol
(18:8:4mL). and stirred for 15 minutes. The layers were
separated and the aqueous layer extracted twice with
dichloromethane. The combined organic layers -were
concentrated in vacuo and the residue purified by flash
chrpmatography (silica gel, gradient
dichloromethane:MeOH) to afford IV-6 as a grey solid
(27mg, 63%): ^ NMR (DMSO) 8 0.88-1.04 (5H, m) , 1.55-1.62
(3H, m), 2.21 (3H, s), 2.70 (2H, m), 3.36 (2H, m), 4.40
(2H, m), 6.37 (1H, s), 7.49 (1H, s), 8.40 (1H, s) , II.92
(1H, br s); MS 288.2 (M+H)+.

Example 379 [5-Amino-6-methyl-2- (4-methylpiperidin-l-yl) -
pyrimidin-4-yl] - (5-methyl-2H-pyrazol-3-yl) -amine (IV-7) :
mp 172-175°C; 1H NMR (DMSO) ? 0.90 (3H, d) , 1.03 (2H, m) ,
1.52-1.62 (3H, m) . 2.13 (3H, s) , 2.20 (3H, s) , 2.69 (2H,
m), 3.92 (2H, br s) , 4.44 (2H, d) , 6.35 (1H, s), 8.41
(1H, S), II.85 (1H, br S) ; IR (solid) 1612, 1589, 1489,
1446, 1317; MS 302.5 (M+H)+.
Example 380 16-Methyl-2- (4-methyl-phenyl) -pyrimidin-4-
yl]- (5-phenyl-2H-pyrazol-3-yl) -amine (IV-10) : MS 342.34
(M+H) ; HPLC-Method E, Rt 1.334 min.
Example 381 [2- (4-Chloro-phenyl) -6-methyl-pyrimidin-4-
yl]-(5-furan-2-yl-2H-pyrazol-3-yl)-amine (IV-II) : MS
352.II (M+H); HPLC Method E, Rt 1.194 min.
Example 382 5-Puran-2-yl-2H-pyrazol—3-yl) - (6-methyl-2-
phenyl-pyrinddin-4-yl)-amine (IV-12) : MS 318.21 (M+H) ;
HPLC-Method E, 1.192 min.
Example 383 [6-Methyl-2- (4-trifluoromethyl-phenyl) -
pyrimidin-4-yl] - (5-phenyl-2-yl-2H-pyrazol—3-yl) -amine
(IV-13) : MS 396.24 (M+H); HPLC-Method E, Rt 1.419 min.
Example 384 (5-Fur an-2-yl-2H-pyrazol—3-yl) - [6 -methyl -2-
(4-trif luoremethyl-phenyl) -pyrimidin-4-yl] -amine (IV-14) :
MS 386.08 (M+H); HPLC-Method E 1.347 min.
Example 385 [2- (2,3-Pihydro-benzo[l,4] dioxin-2-yl) -6-
methyl-pyrimidin-4-yl] - (5-furan-2-yl-2H-pyrazol—3-yl) -
amine (IV-15): MS 376.18 (M+H); HPLC-Method E, Rt 1.181
min.

Example 386 [2- (2,3-Dihydro-bezo[l,4]dioxin-2-yl) -6-
ethyl-pyrimidin-4-yl] - (5-methyl-2ff-pyrazol—3-yl) -amine
(IV-16): MS 338.17 (M+H); HPLC-Method E, Rt 1.082 min.
Example 387 (6-Ethyl-2-phenyl-pyrimidin-4-yl) - (5-methyl-
2H-pyrazol-3-yl) -amine (IV-17) : MS 280.18 (M+H); HPLC-
Method E, Rt 1.024 min.
Example 388 {6-Methyl-2-phenyl-pyrimidin-4-yl) - (5-phenyl-
2H-pyrazol-3-yl)-amine (IV-19) : MS 328.51 (M+H); HPLC-
Method E, Rt 1.192 min.
Example 389 [6-Ethyl-2-(4-trifluoromethy 1 -pheny1)-
pyrimidin- 4 -yl] - (5 -methyl - 2ff-pyrazol—3 -yl) - amine (XV- 20):
MS 348.5 (M+H); HPLC-Method E, Rt 1.224 min.
Example 390 (5-Furan-2-yl-2H-pyrazol—3-yl) - [6-methyl-2-
(4-methyl-pheny1)-pyrimidin-4-yl]-amine (IV-21) : MS
332.23 (M+H); HPLC-Method E, Rt 1.139 min.
Example 391 (6-Methoxymethyl-2-phenyl-pyrimidin-4-yl) - (5-
methyl-2H-pyrazol-3-yl)-amine (IV-22) : MS 296.31 (M+H) ;
HPLC-Method E, Rt 0.971 min.
Example 392 (5,6-Dimethyl-2-phenyl-pyrimidin-4-yl)-(5-
methyl-2H-pyrazol-3-yl) -amine (IV-23) : MS 280.2 (M+H) ;
HPLC-Method E, Rt 0.927 min.
Example 393 (6-Methyl -2 -phenyl -pyrimidin-4 -yl) - (5-methyl-
Zff-pyrazol-3-yl) -amine (XV-24) : MS 266.18 (M+H); HPLC-
Method E, Rt 0.925 min.

Example 394 [6-Ethyl-2- (4-methyl-phenyl) -pyrinidin-4-yl] -
(5-methyl-2H-pyrazol-3-yl)-amine (IV-25): MS 294.46
(M+H); HPLC-Method E, Rt 1.174 min.
Example 395 [2- (4-Chloro-phenyl) -6-ethyl-pyri»idin-4-yl] -
{5-methyl-2ff-pyrazol-3-yl)-amine (IV-26) : MS 314.42
(M+H); HPLC-Metnod E Rt 1.213 min.
Example 396 (5-Methyl-lH-pyrazol-3-yl) - (6-methyl-2-p-
tolyl-pyrimidin-4-yl)-amine (IV-27): MS 280.45 (M+H);
HPLC-Method E, Rt 1.135 min.
Example 397 (JJB-Indazol- 3 -yl) - (6-methoxymethyl-2 -phenyl-
pyrimidin-4-yl)-amine (XV-28) : XH NMR (500 MHz, DMSO) 8
3.57 (3H, s) , 4.65 (2H, s) , 7.23 (1H, J==7.5 Hz, t) , 7.52
(1H, J=7.6 Hz, t), 7.63 (4H, m) , 7.75 (1H, br), 8.13 (1H,
J=5.5 Hz, br d), 8.44 (1H, J=5.7 Hz, br d) , 10.6 (1H,
br), 12.8 (1H, br s) ppm; HPLC-Method A, Rt 2.944 min; MS
(FIA) 332.1 (M+H)+.
Example 398 {5-Methyl-2H-pyrazol-3-yl) - (2-pyxidin-4-yl-
thieno 13,2-d]pyrimidin-4-yl)-amine (IV-29): XH NHR (DMSO)
6 2.34 (3H, s), 6.66 (1H, s), 7.53 (1H, d) , 7.84 (1H, d),
8.32 (2H, d) , 8.70 (2H, d); MS 309.6 (M+H)+.
Example 399 (5-Methyl-2ff-pyrazol-3-yl) - (2-pheayl-
pyrido[3,4-d]pyrimidin -4-yl)-amine (IV-30) : np 225°C; XH
NMR (DMSO) 5 2.35 (3H, s), 6.81 (1H, s), 7.50-7.63 (3H,
m) , 8.45-8.52 (2H, m) , 8.54 (1H, d) , 8.62 (1H, d) , 9.20
(1H, s), 10.79 (1H, s), 12.38 (1H, br B); IR (solid)
2958, 2917, 2852, 1593, 1565, 1524, 1467, 1450; MS 303.2
(M+H) + .

Example 400 (5-Methyl-2H-pyrazol-3-yl) - (2-phenyl-
pyrido[2,3-d]pyrimidin-4-yl)-amine (IV-31) :
To a solution of 4-chloro-2-phenyl-pyrido[2, 3-
d]pyrimidine (J. Pharm. Belg., 29, 1974, 145-148) (109mg,
0.45 mol) in THF (15 mL) was added 3-amino-5-methyl
pyrazole (48 mg, 0.5 mmol) and the resulting mixture
heated at 65 °C overnight. The mixture was cooled to room
temperature and the resulting suspension was filtered and
washed with Et2O. The solid was dissolved in a mixture
EtOH: water and the pH adjusted to pH 7. The aqueous was
extracted twice with ethyl acetate and the combined
organic layers were dried (MgSO4) , filtered, and
concentrated in vacuo. The residue was purified by flash
chromatography (SiO2, DCM-MeOH gradient) to afford IV-31
as an off -white solid (69 mg, 50%): mp 234°C; ^H NMR
(DMSO) 6 2.14 (3H, s), 5.99 (1H, s), 7.20-7.40 (3H, m) ,
7.40-7.50 (3H, m), 8.60 (1H, d), 8.79 (1H, d), 12.82 (1H,
br s) ; IR (solid) 2957, 2921, 2857, 1644, 1560, 1459,
1427; MS 303.2 (M+H)+.
Example 401 (5-Cyclopropyl-2H-pyrazol-3-yl) - (2-phenyl-
pyridor3,4-d]pyrimidin-4-yl)-amine (IV-32) : off-white
solid, mp 232-233°C; ^ NMR (DMSO) 6 0.70-0.85 (2H, m) ,
0.90-1.05 (2H, m) , 1.05-2.07 (1H, m) , 6.75 (1H, s), 7.50-
7.75 (3H, m) , 8.40-8.70 (4H, m), 9.20 (1H, s), 10.80 (1H,
s) , 12.41 (1H); IR (solid) 3178, 1601, 1573, 1532, 1484,
1452, 1409, 1367, 1328, 802, 781, 667; MS 329.2 (M+H)+.
Example 402 [2- (4-Methylpiperidin-l-yl) -purin-4-yl] - (5-
methyl-2H-pyrazol-3-yl) -amine (IV-33) : To a suspension of
2,4-dichloro-purine (2.0 g, 10.6 mmol) in anhydrous
ethanol (10 mL) was added 5-methyl-lH-pyrazol-3-yl amine
(2.05 g, 21.2 mmol) . The resulting mixture was stirred

at room temperature for 48 h. The resulting precipitate
was collected by filtration, washed with ethanol, and
dried under vacuum to afford 1.524 g (58% yield) of (2-
chloro-purin-4-yl) - (5-methyl-lH-pyrazol-3-yl) -amine which
was used in the next step without further purification.
To a solution of (2-chloro-purin-4-yl) - (5-methyl-1H-
pyrazol-3-yl) -amine (200 mg, 0.80 mmol) was added 4-
methylpiperidine (4 mL, 8.01 mmol) and the reaction
mixture heated at reflux overnight. The solvent was
evaporated and the residue dissolved in a mixture
EtOH:water (1:3, 4 mL). Potassium carbonate (57mg, 0.41
mmol) was added and the mixture was stirred at room
temperature for 2 hours. The resulting suspension was
filtered, washed with water (x2) and rinsed with Et2O (x2)
to afford IV-33 as a white solid (225mg, 90%): mp >300°C;
1H NMR (DMSO) ? 0.91 (3H, d), 1.10 (2H, m), 1.65 (3H, m) ,
2.24. (3H, s), 2.84 (2H, m), 4.60 (2H, m) , 6.40 (1H, s),
7.87 (1H, m), 9.37-9.59 (1H, m) , 12.03-12.39, (2H, m); IR
(solid) 1651, 1612, 1574, 1484, 1446, 1327, 1317, 1255,
1203; MS 313.3 (M+H)+.
Example 403 (5-Cydopropyl-2H-pyrazol-3-yl) - [2- (4-
methylpiperidin-1-yl) -pyrrolo[3,2-d]pyrimidin-4-yl] -amine
(IV-34) : white solid; 1H NMR (DMSO) ?-0.65 (2H, m) , 0.91-
0.96 (5H, m), 1.08 (2H, m), 1.58-1.64 (3H, m), 1.89 (1H,
m), 2.77 (2H, t), 4.57 (2H, d), 6.09 (1H, s), 6.38 (1H,
s) , 7.33 (1H, s), 9.42 (1H, s) , 10.65 (1H, s) , 12.02 (1H,
br s); MS 338.3 (M+H)+.
Example 404 [6-Benzyl-2-phenyl-5,6,7,8-tetrahydro-
pyrido [4,3-d]pyrimidin-4-yl] - (5-fluoro-lff-indazol-3-yl) -
amine (IV-35) : 1H NMR (500 MHz, DMSO-d6) ?13.0 (s, 1H) ,
10.4 (s, br, 1H) , 9.73 (s, 1H, TFA-OH) , 8.00 (d, 2H) ,

7.64 (m, 2H) , 7.59 (dd, 1H) , 7.52 (m, 3H) , 7.41 (t, 1H) ,
7.31 (m, 3H), 7.14 (dd, 1H) , 4.58 (s, 2H), 4.35 (br, 2H) ,
3.74 (m, 2H) , 3.17' (s, 2H) ppm. MS (ES+) : m/e= 451.30
(M+H) ; HPLC-Method A, Tret 2.96 min.
Example 405 (5-Fluoro-lS-indazol-3-yl) - (2-pheayl-5, 6,7,8-
tetrahydro-pyrido [4,3-d]pyriioidin-4-yl) -amine (IV-36) :
Prepared from IV-35 (0.13 mmol) by treatment, with an
equal weight of Pd/C (10%) in 4.4% HCOOH in MeOH at room
temperature for 12 h. The mixture was filtered through,
celite, the filtrate was evaporated, and crude product
was purified by HPLC to afford IV-36 as yellow solid in
35% yield. XH NMR (500 MHz, DMSO-d6) 812.9 (s, 1H) , 9.06
(s, 1H) , 7..99 (d, 2H) , 7.57 (dd, 1H) , 7.34 (m, 1H) , 7.28
(m, 3H), 7.22 (d, 1H), 3.83 (s, 2H),. 3.05 (m, 2H), 2.72
(m, 2H) ppm. MS (ES+) : m/e= 361.20 (M+H); HPLC-Method A,
Tret 2.68 min.
Example 406 (5-Methyl-2H-pyrazol—3-yl) - (3 -phenyl-
isoquinolin-1-yl)-amine (V-l) : To a solution of 1-chloro-
3-phenylisoquinoline (J. Het. Chem., 20, 1983, 121-
128) (0.33g, 1.37 mmol) in DMF (anhydrous, 5 mL) was added
3-amino-5-methylpyrazole (0.27g, 2.74 mmol) and potassium
carbonate (0.57g, 4.13 mmol) and the resulting mixture was
heated at reflux for 6 hours. The reaction mixture was
then cooled and solvent removed in vacuo. The residue
was extracted twice with ethyl acetate and the combined
organic layers washed with brine, dried (MgS04) , filtered
and concentrated in vacuo. The crude product was
purified by flash chromatography (SiO2, gradient DCM-MeOH)
to afford V-l as a colourless oil; JH NMR (MeOD) 5 2.23
(3H, s) , 5.61 (1H, s), 7.41 (1H, m), 7.52(2H, m),

7.62 (1H, m) , 7.81(1H, m), 8.07 (1H, d) , 8.19(2H, m) ,
8.29(1H, s) , 8.54 (1H, d) ; MS 301.2 (M+H) + .
Example 407 (lH-Indazol-3-yl) - [3- (2-trifluoromethyl-
phenyl)-isoquinoline-1-yl]-amine (V-2) : A solution of 1-
chloro-3-(2-trifluoronethyl-phenyl)-isoquinoline (100 mg,
0.326 mmol) and lH-indazol-3-ylamine (86 mg, 0.651 ramol)
in ethanbl (3 mL) was heated at 160 C and the solvent
evaporated with a stream of nitrogen. The remaining oil
was then heated at 160 C for 18 hours under nitrogen.
The resulting melt was dissolved in 5%
methanol:dichloromethane (50 mL) , washed with saturated
aqueous sodium bicarbonate (1 x 25 mL) then dried over
magnesium sulfate. Purification by silica gel
chromatography (25% to 50% hexane:ethyl acetate) afforded
V-2 as a yellow solid (35 mg, 27%). 1H NMR.(500 MHz, d6-
DMSO) ? 9.78 (br s, 1H), 8.62 (d, 1H) , 7.9-7.85 (m, 1H) ,
7.78-7.72 (m, 1H), 7.70-7.68 (m, 1H) , 7.65-7.62 (m, 1H) ,
7.60-7.55 (m, 1H) , 7.52-7.45 (m, 3H) , 7.41-7.38 (m, 1H) ,
7.28-7.25 (m, 1H) , 7.18 (s, 1H) , 6.95-6.92 (m, 1H) , 5.76
(s, 1H) ; LC-MS (ES+) m/e= 405.18 (M+H); HPLC-Method D Rt
2.74 min.
Example 408 (5,7-Difluoro-lff-indazol-3-yl) - [3- (2-
trifluorometfcyl-phenyl)-isoquinolin-1-yl] -amine (V-3) :
Prepared from 5,7-difluoro-lH-indazol-3-ylamineto afford
compound V-3 as a yellow solid (90 mg, 63%) . . aH NMR (500
MHz, de-DMSO) 8 13.25 (s, 1H) , 9.92 (br S, 1H) , 8.61 (d,
1H) , 7.9 (d, 1H), 7.81-7.49 (m, 6H) , 7.26-7.2 (m, 2H) ,
7.12-7.10 (m, 1H) ; LC-MS (ES+) m/e= 441.16 (M+H) ; HPLC-
Method D, Rt 3.58 min.

Example 409 (5-Methyl-2H-pyrazol—3-yl) - {2-phenyl-
quinolin-4-yl) -amine (V-4) : To a mixture of 4-chloro-2-
phenylquinoline (J. Het. Chem., 20, 1983, 121-128) (0.53g,
2.21 mmol) in diphenylether (5 mL) was added 3-amino-5-
methylpyrazole (0.43g, -4.42 mmol) and the resulting
mixture heated at 200°C overnight with stirring. The
reaction mixture was cooled to ambient temperature then
petroleum ether (20 mL) was added and the resulting
precipitate was isolated by filtration. The crude solid
was purified by flash chromatography (SiO2, gradient DCM-
MeOH) to afford V-4 as a white solid: mp 242-244°C; aH NMR
(DMSO) 8 2.27(3H, s), 6.02(lH, s), 7.47(2H, d), 7.53-
7.40 (2H) brill), 7.67 (1H, m) , 7.92 (1H, m) , 8'09(2H, d) ,
8.48(2H, m) , 9.2O(1H, s), 12.17(1H, br s); IR (solid)
' 1584, 1559r 1554, 1483, 1447, 1430, 1389; MS 301.2 (M+H)+.
Example 410 (Iff- Xndazol -3-yl)-(2 -phenyl - quinolin- 4 -yl) -
amine (V-5) : XH NMR (500 MHz, de-DMSO) 8 12.78 (s, 1H) ,
9.50 (s, 1H) , 8.65 (d, 1H), 8.15 (s, 1H), 8.04-7.98 (m,
3H) , 7.94 (s, 1H), 7.78-7.75 (m, 1H) , 7.60-7.40 (m, 6H) ,
7.15-7.10 (m, 1H) . LC-MS (ES+) m/e= 337.II (M+H) ; HPLC-
Method D, Rt 2.10 min.
Example 4II (2-Phenyl-quinolin-4-yl) - (lff-pyrazolo[4,3-
b]pyridin-3-yl)-amine (V-6) : *H NMR (500 MHz, DMSO-d6)
813.6 (s, 1H) , II.4 (s, 1H), 8.94 (d, 1H), 8.61 (dd, 1H),
8.23 (d, 1H); 8.16 (dd, 1H), 8.12 (t, 1H), 7.89 (t, 1H) ,
7.86 (d, 1H), 7.65 (m, 4H), 7.54 (s, 1H), 7.52 (dd, 1H)
ppm. MS (ES+) : m/e= 338.II (M+H); HPLC-Method A, HPLC-
Method D, Rt 2.91 min.
Example 412 (lff-Indazol-3-yl)- [2- (2-trifluoromethyl-
phenyl) -quinolin-4-yl] -amine (V-7) : 1H NMR (500 MHz, d6-

DMSO) 5 12.68 (s, 1H), 9.51 (s, 1H), 8.7 (d, 1H) , 7.95-
7.89 (m, 2H), 7.83-7.70 (m, 3H), 7.68-7.62 (m, 2H) , 7.60
(s, 1H), 7.55-7.52 (m, 1H), 7.49-7.45 (m, 1H) , 7.40-7.37
(m, 1H), 7.12-7.09 (m, 1H); LC-MS (ES+) m/e= 405.15
(M+H) ; HPLC-Method D Rt 2.25 min.
Example 413 (5,7-Difluoro-lH-indazol-3-yl)-[2-(2-
trifluoromethyl-phenyl) -quinolin-4-yl] -amine (V-8) : :H NMR
(500 MHz, de-DMSO) 8 13.31 (s, 1H) , 9.4.9 (s, 1H) , 8.70-
8.67 (m, 1H), 7.96-7.92 (m; 1H), 7.85-7.66 (m, 7H), 7.63-
7.60 (m, 1H), 7.42-7.40 (m, 1H) . LC-MS (ES+) m/e= 441.18
(M+H); HPLC-Methpd D Rt 2.39 min.
Example 414 [2- (2-trifluoroxnethyl-phenyl> -quinolin-4-yl] -
(lH-pyrazolo[4,3-b]pyridin-3-yl)-amine (V-9) : JH HMR (500
MHz, DMSO-d6) 513.6 (s, 1H), II.6 (s, br, 1H) , 8.98 (d,
1H) , 8.57 (dd, 1H) , 8.12 (m, 3H), 7.97 (m, 2H), 7.86 (m, ,
3H) , 7.49 (dd, 1H), 7.23 (s, 1H) ppm. MS (ES+): m/e=
406.20 (M+H); HPLC-Method A Rt 2.91 min.
Example 415 (2-Phenyl-quinazolin-4-yl)-(2H-
[1,2,4]triazol-3-yl)-amine (IX-154): off-white solid, mp
266-267C; XH NMR (DMSO) 5 7.50-7.70 (4H, m) , 7.85-8.00
(2H, m), 8.15-8.25 (2H, m), 8.37-8.45 (2H, m), 8.58 (1H,
d), 13.90 (1H, br s); IR (solid) 3344, 3059, 1630, 1609,
1570, 1557, 1543, 1501, 1495, 1445, 14II, 1355, 1326,
1267, II82, 1053, 1038, 760, 676, 667, 654; MS 289.2
(M+H)+.
Example 416 (5-Methyl-2ff-[1,2#4]triazol-3-yl) -(2-phenyl-
quinazolin-4-yl) -amine (IX-155) : XH NMR (500 MHz, DMSO-
d6) 5 8.59 (s, 1H), 8.42 (d, J = 6.7 Hz, 2H), 7.79 (m.

4H), 8.03 (m, 2H), 7.74 (m, 4H), 2.51 (s, 3H) ppm. MS
(ES+): m/e= 303.08 (M+H); HPLC-Method A, Rt 2.64 min.
Example 417 (2H-[1,2,4]-Triazol-3-yl) - 12-(2-
trifluoromethylphenyl) -guinazolin-4-yl] -amine (IX-47) :
Pale yellow solid (52% yield). 1H NMR (500 MHz, DMSO-d6)
? 8.54 (s, 1H), 8.15 (s, br, 1H), 7.91 (t, 1H) , 7.85 (m,
2H) , 7.76 (m, 3H), 7.66 (t, 1H) ppm. MS (ES+) : m/e=
357.13 (M+H); (ES-):m/e= 355.15 (M-H) ; HPLC-Method A, Rt
2.81 min.
Example 418 (5-Methyl-2H- [1/2,4]triazol-3-yl)-[2-(2-
trifluoromethylphenyl) -guinazolin-4-yl] -amine (IX-38) :
Pale yellow solid (54% yield). 1H NMR (500 MHz, DMSO-d6)
?8.44 (s, br, 1H), 7.92 (m, 3H) , 7.84 (m, 1H), 7.77 (m,
2H) , 7.68 (t, 1H), 2.28 (s, 3H) ppm. MS (ES+) : m/e=
371.14 (M+H); (ES-): m/e= 369.18 (M-H); HPLC-Method A, Rt
2.89 min.
Example 419 (5-Methylsulfanyl-2H-[1,2,4]triazol-3-yl)-[2-
(2-trifluorometbylphenyl) -guinazolin-4-yl] -amine (IX-
156): Pale yellow solid (65% yield). 2H NMR (500 MHz,
DMSO-d6) 5 8.56 (br, 1H), 7.90 (t, 1H), 7.84 (m, 2H), 7.78
(m, 2H) , 7.67 (m, 2H) , 2.51 (s, 3H, buried by DMSO) ppm.
MS (ES+): m/e= 403.12 (M+H); (ES-): m/e= 401.16 (M-H);
HPLC-Method A, Rt 3.20 min.
Example 420 (IE-[1,2,4]Triazol-3-yl) -[3-(2-
trifluoromethyl-phenyl)-isoquinolin.-1-yl]-amine (IX-175) :
A solution of l-chloro-3-(2-trifluoromeybyl-phenyl)-
isoquinoline (0.326 mmol) and 2.H- [1,2,4] triazol-3-ylamine
(0.651 mmol) in ethanol (3 mL) was heated at 160°C and
the solvent evaporated with' a stream of nitrogen. The

remaining oil was then heated at 160°C for 18 hours under
nitrogen. The resulting melt was dissolved in 5%
methanol/dichloroinethane (50 mL) , washed with saturated
aqueous sodium bicarbonate (1 x 25 mL) then dried over
magnesium sulfate. Purification by silica gel
chromatography afforded IX-175 as a colorless oil (4%
yield). XH NMR (500 MHz, CDC13) 5 9.18 (d, 1H) , 8.82 (s,
1H), 7.90 (d, 1H), 7.85-7.75 (m, 3H), 7.71-7.62 (m, 3H) ,
7.60-7.55 (m, 2H), 4.42-4.35 (m, 1H). LC-MS (ES+) 356.16
(M+H) ; HPLC-Method D, Rt 3.55 min.
Example 421 (2-Phenyl-quinolin-4-yl) -(Iff-[1,2,4]triazol-
3-yl)-amine (IX-176): Pale yellow solid (30% yield). 2H
NMR (500 MHz, dg-DMSO) 8 13.82 (s, 1H) , 9.91 (S, 1H) ,
8.80 (s, 1H) , 8.70-8.65 (m, 1H),..8.55 (s, 1H) , 8.15-8.12
(m, 2H), 8.03-7.98 (m, 1H), 7.75-7.72 (m, 1H), 7.57-7.49
(m, 3H) . LC-MS (ES+) m/e= 288.II (M+H); HPLC-Method D, Rt
1.55 min.
Example 422 (Iff-[1,2,4]triazol-3-yl)-[2-(2-
trifluoromethyl-phenyl) -quinolin-4-yl] -amine (IX-177) :
Pale yellow solid (46% yield) . XH NMR (500 MHz, ds-DMSO)
8 13.70 (s, 1H), 9.98 (s, 1H), 8.70 (d, 1H), 8.49 (s,
1H), 8.30 (s, 1H), 7.94-7.88 (m, 2H), 7.30-7.68 (m, 3H) ,
7.64-7.56 (m,. 2H) . LC-MS (ES+) m/e= 356.18 (M+H); HPLC-
Method D, Rt 1.68 min.
Example 423 (l-H-Xndazol-3-yl) - [5-methyl-6-morplxolin-4-
yl-2- (2-trifluorometliyl-phenyl) -pyrimidin-4-yl] -amine
(II-251) : Colorless film; 2 % yield; ^-.H-NMR (500 MHz,
CD3OD) 8 7.84 (m, 2H), 7.71 (m, 3H), 7.41 (t, 2H) , 7.14
(m, 1H), 3.74 (m, 4H), 3.69 (m, 4H), 1.24 (s, 3H) ppm;
HPLC-Method A Rt 3.26 min; MS (FIA) 455.1 (M+H).

BIOLOGICAL TESTING
The activity of the compounds as protein kinase
inhibitors may be assayed in vitro, in vivo or in a cell
line. In vitro assays include assays that determine
inhibition of either the phosphorylation activity or
ATPase activity of the activated protein kinase.
Alternate in vitro assays quantitate the ability of the
inhibitor to bind to the protein kinase. Inhibitor
binding may be measured by radiolabelling the inhibitor
prior to binding, isolating the inhibitor/protein kinase
complex and determining the amount of radiolabel bound.
Alternatively, inhibitor binding, may be determined by
running a competition experiment where new inhibitors are
incubated with the protein kinase bound to known
radioligands.
BIOLOGICAL TESTING EXAMPLE 1
Ki DETERMINATION FOR THE INHIBITION OF GSK-3
Compounds were screened for their ability to
inhibit GSK-3P (AA 1-420) activity using a standard
coupled enzyme system (Fox et al. (1998) Protein Sci. 7,
2249). Reactions were carried out in a solution
containing 100 mM HEPES (pH 7.5) , 10 mM MgCl2, 25 mM NaCl,
300 ?M NADH, 1 mM DTT and 1.5% DMSO. Final substrate
concentrations in the assay were 20 ?M ATP (Sigma
Chemicals, St Louis, MO) and 300 ?M peptide
(HSSPHQS(PO3H2)EDEEE, American Peptide, Sunnyvale, CA) .
Reactions were carried out at 30 °C and 20 nM GSK-3?.
Final concentrations of the components of the coupled
enzyme system were 2.5 mM phosphoenolpyruvate, 300 ?M
NADH, 30 ?g/ml pyruvate kinase and 10 ?g/ml lactate
dehydrogenase.

An assay stock buffer solution was prepared
containitig all of the reagents listed above with the
exception of ATP and the test compound of interest. The
assay stock buffer solution (175 ?l) was incubated in a
96 well plate with 5 ?l of the test compound of interest
at final concentrations spanning 0.002 ?M to 3 0 ?M at 30
°C for 10 min. Typically, a 12 point titration was
conducted by preparing serial dilutions (from 10 mM
compound stocks) with DMSO of the test compounds in
daughter plates. The reaction was initiated by the
addition of 20 ?l of ATP (final concentration 20 ?M) .
Rates of reaction were obtained using a Molecular Devices
Spectramax plate reader (Sunnyvale, CA) over 10 min at 30
°C. The Ki values were determined from the rate data as a
function of inhibitor concentration.
The following compounds were shown to have Ki
values less than 0.1 )M for GSK-3: compounds II-l, II-
105, II-33, II-34, II-36, II-39, II-38, II-39, II-40, II-
41, II-42, II-46, II-57, II-59, II-60, II-61, II-62, II-
63, II-64, II-66, II-67, II-69, II-70, II-53, II-71, II-
99, II-73, II-74, II-75, II-76, II-77, II-7, II-8, II-9,
II-10, II-24, II-19, II-78, II-54, II-79, II-80, II-81, .
II-82, II-83, II-84, II-56, II-86, II-20, II-25, II-26,
II-85, II-21; II-27, II-28, II-87, II-88, II-29, II-II,
II-12, II-30, II-31, II-13, II-14, II-15, II-16, II-17,
II-18, II-79, II-23, II-2, II-90, II-91, II-92, II-93,
II-3, II-4, II-5, II-6, II-94, II-95, II-96, II-107, II-
108, II-109, II-II0, II-124, II-125, II-1II, II-II2, II-
II3, II-II4, II-II5, II-II6, II-II7, II-II8, II-II9, II-
120, II-121, II-208, III-8, III-7, III-9, III-37, III-38,
III-39, III-40, III-42, III-45, III-46, III-47, III-48,
III-4-9, III-51, III-52, III-53, III-54, III-55, III-56,
III-57, III-58, III-59, III-60, III-61, III-62, III-63,

III-30, III-65, III-66, III-67, III-70, III-73, III-31,
III-75, III-76, III-77, III-33, III-34, III-1D6, III-108,
III-109, III-lll, III-35, III-II6, III-II7, III-II8, III-
II9, III-120, III-121, III-127, III-128, IU-141, III-
130, III-131, IV-15, IV-16, IV-17, IV-20, IV-25, IV-26,
IV-30, IV-34, V-3, and IX-47.
The following compounds were shown to have K±
values between 0.1 and 1.0 pM for GSK-3: compounds II-
103, II-104, II-35, II-44, II-45, II-49, II-50, II-97,
II-101, II--22, II-32, III-41, III-43, III-44, III-28,
III-50, III-29, III-64, III-71, III-74, IIJ-78, IJI-82,
III-88, III-90, III-102, III-105, III-:i07, III-II0, III-
II2, III-II4, III-II5, III-122, III-124, IXI-124, IV-1,
III-l, III-138, III-140, III-142, III-129, III-132, III-
134, III-135, III-136, IV-1, IV-10, IV-II, IV-12, IV-13,
IV-14, IV-19, IV-21, IV-22, IV-23, IV-24, IV-3, IV-4, IV-
6, IV-7, IV-8, IV-29, IV-31, IV-32, IV-33, IV-36, V-2, V-
7, IX-38, IX-154, and IX-177.
The following compounds were shown to have K±
values between 1.0 and 20 |iM for GSK-3: compounds II-43,
II-65, II-48, II-47, II-51, II-68, II-52, II-72, II-100,
II-98, II-89, III-68, III-81, III-83, III-91, . III-94,
III-95, III-96, III-97, III-98, III-99, III-100, III-101,
III-103, III-123, III-137, III-139, III-143, III-145,
III-146, V-4, V-8, IX-156, and IX-176.
BIOLOGICAL TESTING EXAMPLE 2
KI DETERMINATION FOR INHIBITION OF AURORA-2.
Compounds were screened in the following manner
for their ability to inhibit Aurora-2 vising a standard
coupled enzyme assay (Pox et al (1998) protein Sci 7,
2249).

To an assay stock buffer solution containing
0.1M HEPES 7.5, 10 mM MgCl2, 1 mM DTT, 25 mM NaCl, 2.5 mM
phosphoenolpyruvate, 300 tnM NADH, 30 mg/ml pyruvate
kinase, 10 mg/ml lactate dehydrogenase, 40 mM ATP, and
800 fM peptide (LKRASLG, American Peptide, Sunnyvale, CA)
was added a DMSO solution of a compound of the present
invention to a final concentration of 3 0 JIM. The
resulting mixture was incubated at 30 C for 10 min. The
reaction was initiated by the addition of 10 /xL of
Aurora-2 stock solution to give a final concentration of
70 nM in the assay. The rates of reaction were obtained
by monitoring absorbance at'340 nm over a 5 minute read
time at 30 °C using a BioRad Ultramark plate reader •
(Hercules, CA) . The Ki values were determined from the
rate data as a function of inhibitor concentration.
The following compounds were shown to have Ki
values less than 0.1 |jM for Aurora-2: compounds II-33,
II-34, II-36, II-37, II-40, II-41, II-55, III-7, III-9,
III-37, III-38, III-39, III-40, III-41, III-42, III-44,
III-45, 222-46, III-47, 221-48, III-49, III-50, III-51,
III-52, III-53, 222-54, III-55, III-56, III-57, III-59,
III-60, II2-61, III-63, III-30, III-65, III-66, III-67,
III-70, II2-31, 121-76, 222-77, 222-78, 212-80, 222-32,
222-33, 222-34, 222-106, 122-108, 221-109, II2-II0, 222-
III, II2-II2, III-II4, 122-35, 222-II5, III-II6, 122-II7,
222-II8, 121-II9, III-120,-222-121, 2V-7, 2V-30, 2V-32,
and 2V-34.
The following compounds were shown to have KA
values between 0.1 and 1.0 jiM for Aurora-2: compounds 22-
1, 22-105, 21-35, 22-38, 22-39, 22-42, 21-64, 22-70, 22-
53, 22-99, 21-77, 22-79, 22-86, 22-20, 21-93, 22-94, 222-
28, 122-58, 222-64, 221-71, III-73, III-74, III-75, 222-

102, III-105, III-107, III-II3, III-124, III-l, III-130,
IV-1, IV-3, IV-4, IV-6, IV-29, IV-33, and V-4.
The following compounds were shown to have Ki
values between 1.0 and 20 fiM for Aurora-2: compounds II-
103, II-104., II-57, II-59, II-61, II-63/ II-67, II-69,
II-75, II-76, II-10, II-19, II-78, II-54, II-80, II-.82,
II-21, II-90, II-91, II-96, II-107, III-68, III-79, III-
82, III-101, III-103, III-127, III-141, III-129, III-132,
IV-31, V-2, IX-47, IX-154, and IX-177.
BIOLOGICAL TESTING EXAMPLE 3
CDR-2 INHIBITION ASSAY '
Compounds were screened in the following manner
for their ability to inhibit CDK-2 using a standard
coupled enzyme assay (Fox et al (1998) Protein Scl 7,
2249).
To an assay stock buffer solution containing
0.1M HEPES 7.5, 10 mM MgCl2, 1 mM DTT, 25 mM NaCl, 2.5 mM
phosphoenolpyruvate, 300 mM NADH, 30 mg/ml pyruvate
kinase, 10 mg/ml lactate dehydrogenase, 100 mM ATP, and
100 /zM peptide (MAHHHRSPRKRAKKK, American Peptide,
Sunnyvale, CA) was added a DMSO solution of a compound of
the present invention to a final concentration of 30 /xM.
The resulting mixture was incubated at 30 °C for 10 min.
The reaction was initiated by the addition of
10 /iL of CDK-2/Cyclin A stock solution to give a final
concentration of 25 nM in the assay. The rates of
reaction were obtained by monitoring absorbance at 340 nm
over a 5-minute read time at 30 °C using a BioRad
Ultramark plate reader (Hercules, CA) . The Ki values were
determined from the rate data as a function of inhibitor
concentration.

BIOLOGICAL TESTING EXAMPLE 4
ERK INHIBITION ASSAY
Compounds were assayed for the inhibition of
KRK2 by a spectrophotometric coupled-enzyme assay (Fox et
al (1998) Protein Sci 7, 2249). In this assay, a fixed
concentration of activated ERK2 (10 nM) was incubated
with various concentrations of the compound in DMSO (2.5
%) for 10 min. at 30°C in 0.1 M HEPES buffer, pH 7.5,
containing 10 mM MgCl2, 2.5 mM phosphoenolpyruvate, 200
?M NADH, 150 ?g/mL pyruvate kinase, 50 ?g/mL lactate
dehydrogenase, and 200 fM erktide peptide. The reaction
was initiated by the addition of 65 jzM ATP. The rate of
decrease of absorbance at 340 nM was monitored. The ICS0
was evaluated from the rate data as a function of
inhibitor concentration.
The following compounds were shown to have a Ki
value of II7, III-II8, III-120, and IV-4. '
The following compounds were shown to have a Ki
value of between lyM and 12pM for ERK-2: III-63, III-40,
and III-108.
BIOLOGICAL TESTING EXAMPLE 5
AKT INHIBITION ASSAY
Compounds were screened for their ability to
inhibit AKT using a standard coupled enzyme assay (Fox et
al., Protein Sci., (1998) 7, 2249). Assays were carried
out in a mixture of 100 mM HEPES 7.5, 10 mM MgC12, 25 mM
NaCl , 1 mM DTT and 1.5% DMSO. Final substrate
concentrations in the assay were 170 fM. ATP (Sigma
Chemicals) and "200 fM peptide (RPRAATF, American Peptide,
Sunnyvale, CA) . Assays were carried out at 3-0 . C and 45
nM AKT. Final concentrations of the components of the

coupled enzyme system were 2.5 mM phosphoenolpyruvate,
300 /iM NADH, 30 /ig/ML pyruvate kinase and 10 fig /ml
lactate dehydrogenase.
An assay stock buffer solution was prepared
containing all of the reagents listed above, with the
exception of AKT, DTT, and the test compound of interest.
56 jil of the- stock solution was placed in a 384 well
plate followed by addition of 1 jil of 2 mM DMSO stock
containing the test compound {final compound
concentration 3 0 /zM) . The plate was preincubated for
about 10 minutes at 30 C and the reaction initiated by
addition of 10 fil of enzyme (final concentration 45 nM)
and 1 mM DTT.- Rates of reaction were obtained using a
BioRad Ultramark plate reader (Hercules, CA) over a 5-
minute read time at 3 0 C. Compounds showing greater than
50% inhibition versus standard wells containing the assay
mixture and DMSO without test compound were titrated to
determine IC50 values.
BIOLOGICAL TESTING EXAMPLE 6
SRC INHIBITION ASSAY
The compounds were evaluated as inhibitors of
human Src kinase using either a radioactivity-based assay
or spectrophotometric assay.
Src Tin^*1'1'!"'?* *-?Pn Agsay A: Radioactivity-based Assay
The compounds were assayed as inhibitors of
full length recombinant human Src kinase (from Upstate
Biotechnology, cat. no. 14-II7) expressed and purified
from baculo viral cells. Src kinase activity was
monitored by following the incorporation of 33P from ATP
into the tyrosine of a random poly Glu-Tyr polymer
substrate of composition, GlurTyr =4:1 (Sigma, cat. no.
P-0275) . The following were the final concentrations of
the assay components: 0.05 M HEPES, pH 7.6, 10 mM MgCl2, 2

mM DTT, 0.25 mg/ml BSA, 10 (iM ATP (1-2 fiC± 33P-ATP per
reaction) , 5 mg/ml poly Glu-Tyr, and 1-2 units of
recombinant human Src kinase. In a typical assay, all
the reaction components with the exception of ATP were
pre-mixed and aliquoted into assay plate wells.
Inhibitors dissolved in DMSO were added to the wells to
give a final DMSO concentration of 2.5%. The assay plate
was incubated at 30 °C for 10 min before initiating the
reaction with 3JP-ATP. After 20 min of- reaction, the
reactions were quenched with 150 fil of 10%
trichloroacetic acid (TCA) containing 20 mM Na3PO4. The
quenched samples were then transferred to a 96-well
filter plate (Whatman, UNI-Filter GF/F Glass Fiber
Filter, cat no. 7700-3310) installed on a filter plate
.vacuum manifold. Filter plates were washed four.times
with 10% TCA containing 20 mM Na3PO4 and then 4 times with
methanol. 200/tl of scintillation fluid was then added to
each well. The plates were sealed and the amount of
radioactivity associated with the filters was quantified
on a TopCount scintillation counter. The radioactivity
incorporated was plotted as a function of the inhibitor
concentration. The data was fitted to a competitive
inhibition kinetics model to get the K± for the compound.
Src Inhibition Assay B; Spectrophotometric Assay
The ADP produced from ATP by the human
recombinant Src kinase-catalyzed phosphorylation of poly
Glu-Tyr substrate was quanitified using a coupled enzyme
assay (Fox et al (1998) Protein Sex 7, 2249). In this
assay one molecule of NADH is oxidised to NAD for every
molecule of ADP produced in the kinase reaction. The
disappearance of NADH can be conveniently followed at 340
nm.

The following were the final concentrations of
the assay components: 0.025 M HEPES, pH 7.6, 10 mM MgCl2,
2 mM DTT, 0.25 mg/ml poly Glu-Tyr, and 25 nM of
recombinant human Src kinase. Final concentrations of the
components of the coupled enzyme system were 2.5 mM
phosphoenolpyruvate, 200 ?M NADH, 30 Kg/ml pyruvate
kinase and 10 jig/ml lactate dehydrogenase.
In a typical assay, all the reaction components
with the exception of ATP were pre-mixed and aliquoted
into assay plate wells. Inhibitors dissolved in DMSO
were added to the wells to give a filial DMSO' concentration
of 2.5%. The assay plate was incubated at 30 C for 10 tnin
before initiating the reaction with 100 juM ATP. The
absorbance change at 340 nm with time, the rate of the
reaction, was monitored on a molecular devices plate
reader. The data of rate as a function of the inhibitor
concentration was fitted to compettive inhibition
kinetics model to get the KA for the compound.
The following compounds were shown to have a Ki
value of .III-35, III-47, III-65, III-66, III-37, III-38,III-39,
III-40, III-42, III-44, III-48,. III-49, III-70, III-45,
III-78, III-76, and IV- 32.
The following compounds were shown to have a Ki
value of between lOOnM and lyM for SRC: III-63, III-71,
III-75, III-73, III-72, III-74, III-80, III-50, IV-30.
The following compounds were shown to have a K±
value of between 1^ and 6fiM for SRC: III-79, IV-1, and
IV-31.
While we have hereinbefore presented a number
of embodiments of this invention, it is apparent that our
basic construction can be altered to provide other
embodiments which utilize the compounds and methods of

this invention. Therefore, it will be appreciated that
the scope of this invention is to be defined by the
appended claims rather than by the specific embodiments
which have been represented by way of example.

WE CLAIM:
1. A compound of formula II:

or a pharmaceutically acceptable derivative or prodrug
thereof, wherein;
Ring C is selected from a phenyl, pyridinyl, pyrimidinyl,
pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring,
wherein said Ring C has one or two ortho substituents
independently selected from -R1, any substitutable non-
ortho carbon position on Ring C is independently
substituted by -R5, and two adjacent substituents on
Ring C are optionally taken together with their
intervening atoms to form a fused, unsaturated or
partially unsaturated, 5-6 membered ring having 0-3
heteroatoms selected from oxygen, sulfur or nitrogen,
said fused ring being optionally substituted by halo,
oxo, or -R8;
R1 is selected from -halo, -CN, -NO2, T-V-R6, phenyl, 5-6
membered heteroaryl ring, 5-6 membered heterocyclyl
ring, or C1-6 aliphatic group, said phenyl, heteroaryl,
and heterocyclyl rings each optionally substituted by
up to three groups independently selected from halo,
oxo, or -R8, said C1-6 aliphatic group optionally
substituted with halo, cyano, nitro, or oxygen, or R1
and an adjacent substituent taken together with their
intervening atoms form said ring fused to Ring C;
Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 0-3 ring heteroatoms selected from

oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
substituted by oxo or T-R3, and any substitutable
nitrogen on said ring formed by Rx and RY is substituted
by R4;
T is a valence bond or a C1-4 alkylidene chain;
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -NO?, -R7, or
-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -NO2, -CN, -S(O)R, -S(O)2R, -SR, -N
(R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7)
CO2(d-6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N
(R7)CON(R7)2, -N(R7)SO2N(R7)2, -N(R4)SO2R, or -0C(=O)N(R7)
2!
each R is independently selected from hydrogen or an
optionally substituted group selected from C!-6
aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring
atoms, or a heterocyclyl ring having 5-10 ring atoms;
each R4 is independently selected from -R7, -COR7, -CO2
(optionally substituted C1-6 aliphatic) , -CON(R7)2, or
-SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring;
each R5 is independently selected from -R, halo, -OR, -C
(=O)R, -CO2R, -COCOR, -NO2, -CN, -S (O) R, -SO2R, -SR, -N
(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)
CO2 (optionally substituted Ci-6 aliphatic) , -N (R4) N (R4) 2,
-C=NN(R4)2,' -C=N-OR, -N(R4)CON(R4)2, -N (R4) SO2N (R4) 2, -N
(R4)SO2R, or -OC (=O)N(R4)2, or R5 and an adjacent

substituent taken together with their intervening atoms
form said ring fused to Ring C;
V is -0-, -S-, -SO-, -S02-, -N(R6)SO2-, -SO2N(R6)-, -N(R6)-,
-CO-, -CO2-, -N(R6)CO-, -N(R6)C(O)O-, -N (R6) CON (R6) -, -N
(R6)SO2N(R6)-, -N(R6)N(R6)-, -C(O)N(R6)-, -0C (0) N (R6)-, -C
(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N
(R6)-, -C(R6)2N(R6)-, -C(R6)2N(R6)C(O)-, -C (R6) 2N (R6) C (0)
0-, -C(R6)=NN(R5)-, -C(R6)=N-O-, -C (R6) 2N (R6) N (R6)-, -C
(R6)2N(R6)SO2N(R6)-/ or -C (R6) 2N (R6) CON (R6)-;
W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)
2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -C02-, -C (R6) OC (0) -, -C
(R6)OC(O)N(R6)-, -C(R6)2N(R6)CO-, -C (R6) 2N (R6) C (0) 0-,' -C
(R6)=NN(R6)-, -C(R6)==N-O-, -C (R6) 2N (R6) N (R6)-, -C(R6)2N(R6)
SO2N(R6)-, -C(R6)2N(R6)CON(R6)-, or -CON(R6)-;
each R6 is independently selected from hydrogen, or an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring;
each R7 is independently selected from hydrogen or an
optionally substituted Ci-6 aliphatic group, or two R7 on
the same nitrogen are taken together with the nitrogen
to form a 5-8 membered heterocyclyl or heteroaryl ring;
and
each R9 is independently selected from an optionally
substituted C1-4 aliphatic group, -OR6, -SR6, -COR6,
-SO2R6, -N(R6)2, -N(R6)N(R6)2, -CN, -N02, -CON(R6)2, or
-CO2R6.
2. The compound as claimed in claim 1, wherein said
compound has one or more features selected from the group
consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from an

optionally substituted naphthyl, quinolinyl or
isoquinolinyl ring;
(b) Rx is hydrogen or C1-4 aliphatic and Ry is
T-R3, or Rx and Ry are taken together with their
intervening atoms to form an optionally substituted 5-7
membered unsaturated or partially unsaturated ring having
0-2 ring nitrogens;
(c) R1 is -halo, an optionally substituted C1-6
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R6, -SO2NH2,
-N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; and
(d) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl,
heteroaryl, or a Ci-6 aliphatic group, or R2 and R2' are
taken together with their intervening atoms to form a
substituted or unsubstituted benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring.
3. The compound as claimed in claim 2, wherein:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from an
optionally substituted naphthyl, quinolinyl or
isoquinolinyl ring;
(b) Rx is hydrogen or C1-4 aliphatic and Ry is
T-R3, or Rx and Ry are taken together with their
intervening atoms to form an optionally substituted 5-7
membered unsaturated or partially unsaturated ring having
0-2 ring nitrogens;
(c) R1 is -halo, an optionally substituted C1-6
aliphatic group, phenyl, -COR6, -OR6, -CN, -SO2R5, -SO2NH2,
-N(R6)2, -CO2R6, -CONH2, -NHCOR6, -OC(O)NH2, or -NHSO2R6; and
(d) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl,
heteroaryl, or a C1-6 aliphatic group, or R2 and R2' are
taken together with their intervening atoms to form a
(b)
substituted or unsubstituted benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring.
4. The compound as claimed in claim 2, wherein said
compound has one or more features selected from the group
consisting of:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring
system, the bicyclic ring system is selected from an
optionally substituted naphthyl ring;
(b) Rx is hydrogen or methyl and Ry is -R, N(R4)
2, or -OR, or Rx and Ry are taken together with their
intervening atoms to form a 5-7 membered unsaturated or
partially unsaturated carbocyclo ring optionally
substituted with -R, halo, -OR, -C(=O)R, -CO2R, -COCOR,
-N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)
2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted Ci-
6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N(R4)CON
(R4)2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -0C (=0) N (R4) 2, ;
(c) R1 is -halo, a Ci-6 haloaliphatic group, a C1-6
aliphatic group, phenyl, or -CN;
(d) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl, or
a Ci-6 aliphatic group, or R2 and R2' are taken together
with their intervening atoms to form a substituted or
unsubstituted benzo, pyrido, pyrimido or partially
unsaturated 6-membered carbocyclo ring; and
(e) each R5 is independently selected from
-halo, -CN, -N02, -N(R4)2, optionally substituted C1-6
aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR,
-SO2N(R4)2, and -N(R4)SO2R.
5. The compound as claimed in claim 4, wherein:
(a) Ring C is a phenyl or pyridinyl ring,
optionally substituted by -R5, wherein when Ring C and two
adjacent substituents thereon form a bicyclic ring

system, the bicyclic ring system is selected from an
optionally substituted naphthyl ring;
(b) R- is hydrogen or methyl and Ry is -R, N(R^)
2, or -OR, or Rx and Ry are taken together with their
intervening atoms to form a 5-7 membered unsaturated or
partially unsaturated carbocyclo ring optionally
substituted with -R, halo, -OR, -C(=O)R, -CO2R, -COCOR,
-N02, -CN, -S(O)R, -SO2R, -SR, -N(R4)2, -CON(R4)2, -SO2N(R4)
2, -OC(=O)R, -N(R4)COR, -N(R4)CO2 (optionally substituted Ci-
6 aliphatic) , -N (R4) N (R4) 2, -C=NN(R4)2, -C=N-OR, -N(R4)CON
(R4)2, -N(R4)SO2N(R4)2, -N(R4)SO2R, or -0C (=0) N (R4) 2, ;
(c) R1 is -halo, a C1-6 haloaliphatic group, a Ci-6
aliphatic group, phenyl, or -CN;
(d) R2' is hydrogen and R2 is hydrogen or a
substituted or unsubstituted group selected from aryl, or
a C1-6 aliphatic group, or R2 and R2' are taken together
with their intervening atoms to form a substituted or
unsubstituted benzo, pyrido, pyrimido or partially
unsaturated 6-membered carbocyclo ring; and
(e) each R5 is independently selected from
-halo, -CN, -N02, -N(R4)2, optionally substituted C1-6
aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R4), -N(R4)COR,
-SO2N(R4)2, and -N(R4)SO2R.
6. The compound as claimed in claim 4, wherein said
compound has one or more features selected from the group
consisting of:
(a) Rx is hydrogen or methyl and Ry is methyl,
methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl,
alkyl- or an optionally substituted group selected from
2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry
are taken together with their intervening atoms to form a
6-membered unsaturated or partially unsaturated
carbocyclo ring optionally substituted with -halo, -R,
-OR, -COR, -CO2R, -CON(R4)2/ -CN, or -N(R4)2 wherein R is
an optionally substituted C1-6 aliphatic group;

(b) R1 is -halo, a C1-4 aliphatic group
optionally substituted with halogen, or -CN;
(c) R- ana R-' are taken together with their
intervening atoms to form a benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring
optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -C1-
4 haloalkyl, -N02, -0 (C1-4 alkyl) , -C02 (C1-4 alkyl) , -CN, -S02
(C1-4 alkyl), -SO2NH2, -0C(0)NH2/ -NH2SO2 (C1-4 alkyl) , -NHC(O)
(C1-4 alkyl), -C(0)NH2, or -CO (d-4 alkyl), wherein the (C1-4
alkyl) is a straight, branched, or cyclic alkyl group;
and
(d) each R5 is independently selected from -Cl,
-F, -CN, -CF3, -NH2, -NH(Ci-4 aliphatic), -N(d-4 aliphatic)
2, -0(C1-4 aliphatic), Ci-4 aliphatic, and -CO2(Ci_j
aliphatic) .
7. The compound as claimed in claim 6, wherein:
(a) Rx is hydrogen or methyl and Ry. is methyl,
methoxymethyl, ethyl, cyclopropyl, isopropyl, t-butyl,
alkyl- or an optionally substituted group selected from
2-pyridyl, 4-pyridyl, piperidinyl, or phenyl, or Rx and Ry
are taken together with their intervening atoms to form a
benzo ring or a partially unsaturated carbocyclo ring
optionally substituted with -halo, -R, -OR, -COR, -CO2R,
-CON(R4)2/ -CN, or -N(R4)2 wherein R is an optionally
substituted d_6 aliphatic group;
(b) R1 is -halo, a C1-4 aliphatic group
optionally substituted with halogen, or -CN;
(c) R2 and R2' are taken together with their
intervening atoms to form a benzo, pyrido, pyrimido or
partially unsaturated 6-membered carbocyclo ring
optionally substituted with -halo, -N(R4)2, -C1-4 alkyl, -Ci_
4 haloalkyl, -N02, -0 (d-4 alkyl) , -C02 (d-4 alkyl) , -CN, -S02
(d-4 alkyl), -SO2NH2, -OC(O)NH2, -NH2SO2 (d-4 alkyl) , -NHC(O)
(C1-4 alkyl), -C(0)NH2, or -CO (C1-4 alkyl) , wherein the (d-4
alkyl) is a straight, branched, or cyclic alkyl group;
and
(a)
(d) each R5 is independently selected from -Cl,
-F, -CN, -CF3, -NH2, -NH(C1-4 aliphatic), -N(C1-4 aliphatic)
i, -O(C1-4 aliphatic), C1-4 aliphatic, and -CO2(C1-4
aliphatic).
8. The compound as claimed in claim 7, wherein Rx
and Ry are each methyl or R* and Ry are taken together
with the pyrimidine ring to form an optionally
substituted ring selected from quinazoline or
tetrahydroquinazoline, and R2 and R2' are taken together
with the pyrazole ring to form an optionally substituted
indazole ring.
9. The compound as claimed in claim 1, wherein said
compound is selected from Table 1.
10. A composition comprising a compound as claimed
in any one of claims 1-9 and a pharmaceutically
acceptable carrier such as herein described.
II. The composition as claimed in claim 10, having
a second therapeutic agent, such as herein described.
12. A pharmaceutical composition as claimed in
claim 10, which is capable of being used for treating
diabetes, Alzheimer's disease, Huntington's Disease,
Parkinson's Disease, AIDS-associated dementia,
amyotrophic lateral sclerosis (AML), multiple sclerosis
(MS), schizophrenia, cardiomycete hypertrophy,
reperfusion/ischemia, baldness, or a cancer selected from
breast, ovary, cervix, prostate, testis, genitourinary
tract, esophagus, larynx, glioblastoma, neuroblastoma,
stomach, skin, keratoacanthoma, lung, epidermoid
carcinoma, large cell carcinoma, small cell carcinoma,
lung adenocarcinoma, bone, colon, adenoma, pancreas,
adenocarcinoma, thyroid, follicular carcinoma,
undifferentiated carcinoma, papillary carcinoma,

seminoma, melanoma, sarcoma, bladder carcinoma, liver
carcinoma and biliary passages, kidney carcinoma, myeloid
disorders, lymphoid disorders, Hodgkin's, hairy cells,
buccal cavity and pharynx (oral), lip, tongue, mouth,
pharynx, small intestine, colon-rectum, large intestine,
rectum, brain and central nervous system, and leukemia.
13. A method of inhibiting GSK-3 or Aurora activity
in a biological sample comprising contacting said
biological with the compound as claimed in claim 1.
14. A pharmaceutical composition as claimed in
claim 10, which is capable of being used for treating
diabetes, Alzheimer's disease, Huntington's Disease,
Parkinson's Disease, AIDS-associated dementia,
amyotrophic lateral sclerosis (AML), multiple sclerosis
(MS), schizophrenia, cardiomycete hypertrophy,
reperfusion/ischemia, and baldness.
15. The pharmaceutical composition as claimed in
claim 14, which has a second therapeutic agent, such as
herein described.
16. The pharmaceutical composition as claimed in
claim 14, wherein said disease is diabetes.
17. The pharmaceutical composition as claimed in
claim 14, wherein said disease is Alzheimer's disease.
18. The pharmaceutical composition as claimed in
claim 14, wherein said disease is schizophrenia.
19. The pharmaceutical composition as claimed in
claim 10, which is capable of being used for enhancing
glycogen synthesis in a patient in need thereof.
20. The pharmaceutical composition as claimed in
claim 10, which is capable of being used for lowering
blood levels of glucose in a patient in need thereof.

21. The pharmaceutical composition as claimed in
claim 10, which is capable of being used for inhibiting
the production of hyperphosphorylated Tau protein in a
patient in need thereof.
22. The pharmaceutical composition as claimed in
claim 10, which is capable of being used for inhibiting
the phosphorylation of (5-catenin in a patient in need
thereof.
23. A pharmaceutical composition as claimed in
claim 10, which is capable of being used for treating a
cancer selected from breast, ovary, cervix, prostate,
testis, genitourinary tract, esophagus, larynx,
glioblastoma, neuroblastoma, stomach, skin,
keratoacanthoma, lung, epidermoid carcinoma, large cell
carcinoma, small cell carcinoma, lung adenocarcinoma,
bone, colon, adenoma, pancreas, adenocarcinoma, thyroid,
follicular carcinoma, undifferentiated carcinoma,
papillary carcinoma, seminoma, melanoma, sarcoma, bladder
carcinoma, liver carcinoma and biliary passages, kidney
carcinoma, myeloid disorders, lymphoid disorders,
Hodgkin's, hairy cells, buccal cavity and pharynx (oral),
lip, tongue, mouth, pharynx, small intestine, colon-
rectum, large intestine, rectum, brain and central
nervous system, and leukemia.
24. The pharmaceutical composition as claimed in
claim 23, which has a second therapeutic agent, such as
herein described.
25. The pharmaceutical composition as claimed in
claim 23, wherein said disease is melanoma or is selected
from colon, lung, stomach, or breast cancer.
26. A compound of formula A:
23.

wherein:
R1 is selected from CF3;
R5 is one to three substituents that are each
independently selected from H, Cl, F, CF3, N02, or CN,
provided that R1 and Rs are not simultaneously Cl;
Rx and Rv are independently selected from T-R3, or Rx and
RY are taken together with their intervening atoms to
form, a fused, unsaturated or partially unsaturated, 5-8
membered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by R* and Ry is
optionally and independently substituted by T-R3, and

any substitutable nitrogen on said ring formed by Rx
and Ry is substituted by R4;
T is a valence bond or a d-4 alkylidene chain;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -N02, -CN, -S (O) R, -S(O)2R, -SR, -N
(R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7)
CO2 (optionally substituted C1-6 aliphatic) , -N (R4) N (R4) 2,
-C=NN(R4)2, -C=N-OR, -N(R7)CON(R7)2/ -N (R7) SO2N (R7) 2, -N
(R4)SO2R, or -OC(=O)N(R7)2;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6_i0 aryl, a heteroaryl ring having 5-10 ring
atoms, or a heterocyclyl ring having 5-10 ring atoms;
each R4 is independently selected from -R7, -COR7, -CO2
(optionally substituted C1-6 aliphatic) , -CON(R7)2, or
-SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring; and
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7 on
the same nitrogen are taken together with the nitrogen
to form a 5-8 membered heterocyclyl or heteroaryl ring.

wherein:
R2 and R2' are independently selected from -R, -T-W-R6, or
R2 and R2' are taken together with their intervening
atoms to form a fused, 5-8 membered, unsaturated or
partially unsaturated, ring having 0-3 ring heteroatoms
selected from nitrogen, oxygen, or sulfur, wherein each
substitutable carbon on said fused ring formed by R2
and R2' is substituted by halo, oxo, -CN, -N02, -R7, or

-V-R6, and any substitutable nitrogen on said ring
formed by R2 and R2' is substituted by R4;
Rx and Ry are independently selected from T-R~, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
optionally and independently substituted by T-R3, and
any'substitutable nitrogen on said ring formed by Rx
and Ry is substituted by R4;
T is a valence bond or a C1-4 alkylidene chain;
V is -O-, -S-, -SO-, -SO2-, -N(R6)SO2-, -SO2N(R6)-, -N(R6)-,
-CO-, -CO2-, -N(R6)CO-, -N(R6)C(O)0-, -N (R6) CON (R6) -, -N
(R6)SO2N(R6)-, -N(R6)N(R6)-, -C(O)N(R6)-, -OC (O) N (R6) -, -C
(R6)2O-, -C(R6}2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)2SO2N
(R6)-, -C(R6)2N(R6)-, -C(R6)2N(R6)C(O)-, -C (R6) 2N (R6) C (O)
O-, -C(R6)=NN(R6)-, -C(R6)=N-O-, -C (R6) 2N (R6) N (R6)-, -C
(R6)2N(R6)SO2N(R6)-, or -C (R6) 2N (R6) CON (R6) -;
W is -C(R6)2O-, -C(R6)2S-, -C(R6)2SO-, -C(R6)2SO2-, -C(R6)
2SO2N(R6)-, -C(R6)2N(R6)-, -CO-, -CO2-, -C (R6) OC (0)-, -C
(R6)OC(O)N(R6)-, -C(R6)2N(R6)CO-, -C (R6) 2N (R6) C (0) 0-, -C
(R6)=NN(R6)-, -C(R6)=N-O-, -C (R6) 2N (R6) N (R6)-, -C(R6)2N(R6)
SO2N(R6)-, -C(R6)2N(R6)CON(R6)-, or -CON(R6)-;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -N02, -CN, -S(O)R, -S(O)2R, -SR, -N
(R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)C0R, -N(R7)
C02 (optionally substituted d-6 aliphatic) , -N (R4) N (R4) 2,
-C=NN(R4)2, -C=N-OR, -N(R7)CON(R7)2, -N (R7) SO2N (R7) 2, -N
(R4)SO2R, or -OC(=O)N(R7)2;
each R is independently selected from hydrogen or an
optionally substituted group selected from Ci-6
aliphatic, C6-io aryl, a heteroaryl ring having 5-10 ring
atoms, or a heterocyclyl ring having 5-10 ring atoms;
each R4 is independently selected from -R7, -COR7, -CO2
(optionally substituted C1-6 aliphatic) , -CON(R7)2, or
-SO2R7, or two R4 on the same nitrogen are taken

together to form a 5-8 membered heterocyclyl or
heteroaryl ring.
each R' is independently selected from hydrogen or an
optionally substituted C1-4 aliphatic group, or two R6
groups on the same nitrogen atom are taken together
with the nitrogen atom to form a 5-6 membered
heterocyclyl or heteroaryl ring; and
each R7 is independently selected from hydrogen or an
optionally substituted C1-6 aliphatic group, or two R7 on
the: same nitrogen are taken together with the nitrogen
to form a 5-8 membered heterocyclyl or heteroaryl ring
with the proviso that R2 is other than t-butyl and R2 is
other than methyl when Rx is Br, Ry is H, R2' is H.
29. The compound as claimed in claim 28, wherein Rx
and Ry are each methyl, or Rx and Ry are taken together
with the pyrimidine ring to form a quinazoline or
tetrahydroquinazoline ring.
30. The compound as claimed in claim 29, wherein R2
and R2' are taken together with the pyrazole ring to form
an indazole ring.

wherein:
Rx and Ry are independently selected from T-R3, or Rx and
Ry are taken together with their intervening atoms to
form a fused, unsaturated or partially unsaturated, 5-8
membered ring having 0-3 ring heteroatoms selected from
oxygen, sulfur, or nitrogen, wherein any substitutable
carbon on said fused ring formed by Rx and Ry is
optionally and independently substituted by T-R3, and

any substitutable nitrogen on said ring formed by is
substituted by R4;
T is a valence bond or a C1-4 alkylidene chain;
R3 is selected from -R, -halo, -OR, -C(=O)R, -CO2R,
-COCOR, -COCH2COR, -N02, -CN, -S(O)R, -S(O)2R, -SR, -N
(R4)2, -CON(R7)2, -SO2N(R7)2, -OC(=O)R, -N(R7)COR, -N(R7)
CO2 (optionally substituted C1-6 aliphatic) , -N (R4) N (R4) 2,
-C==NN(R4)2, -C=N-OR, -N(R7)CON(R7)2, -N (R7) SO2N (R7) 2, -N
(R4)SO2R, or -OC(=O)N(R7)2;
each R is independently selected from hydrogen or an
optionally substituted group selected from C1-6
aliphatic, C6-io aryl, a heteroaryl ring having 5-10 ring
atoms, or a heterocyclyl ring having 5-10 ring atoms;
each R4 is independently selected from -R7, -COR7, -CO2
(optionally substituted C^ aliphatic) , -CON(R7)2, or
-SO2R7, or two R4 on the same nitrogen are taken
together to form a 5-8 membered heterocyclyl or
heteroaryl ring; and
each R5 is independently selected from -R, halo, -OR, -C
(=O)R, -CO2R, -COCOR, -NO2, -CN, -S (0) R, -SO2R, -SR, -N
(R4)2, -CON(R4)2, -SO2N(R4)2, -OC(=O)R, -N(R4)COR, -N(R4)
CO2 (optionally substituted Ci-6 aliphatic) , -N (R4) N (R4) 2,
-C=NN(R4)2, -C=N-OR, -N(R4)CON(R4)2, -N (R4) SO2N (R4) 2, -N
(R4)SO2R, or -OC(=O)N(R4)2
each R7 is independently selected from hydrogen or an
optionally substituted Ci-6 aliphatic group, or two R7 on
the same nitrogen are taken together with the nitrogen
to form a 5-8 membered heterocyclyl or heteroaryl ring.
32. The compound as claimed in claim 31, wherein Rx
and Ry are each methyl, or Rx and Ry are taken together
with the pyrimidine ring to form a quinazoline or
tetrahydroquinazoline ring.
This invention describes novel pyrazole compounds of formula II: wherein Ring C is selected from a phenyl, pyridinyl,
pyrimidinyl, pyridazinyl, pyrazinyl, or 1, 2, 4-triazinyl ring, and R2, R2, Rx, and Ry are as described in the specification. Ring C has
an ortho substituent and is optionally substituted in the non-ortho positions. R2 and R2 are optionally taken together with their intervening
atoms to form a fused ring system, such as an indazole ring; and Rx and Ry are optionally taken together with their intervening
atoms to form a fused ring system, such as a quinazoline ring. The compounds are useful as protein kinase inhibitors, especially as

Documents:

295-KOLNP-2003-FORM 27-1.1.pdf

295-KOLNP-2003-FORM-27-1.1.pdf

295-KOLNP-2003-FORM-27.pdf

295-kolnp-2003-granted-abstract.pdf

295-kolnp-2003-granted-assignment.pdf

295-kolnp-2003-granted-claims.pdf

295-kolnp-2003-granted-correspondence.pdf

295-kolnp-2003-granted-description (complete).pdf

295-kolnp-2003-granted-examination report.pdf

295-kolnp-2003-granted-form 1.pdf

295-kolnp-2003-granted-form 18.pdf

295-kolnp-2003-granted-form 2.pdf

295-kolnp-2003-granted-form 3.pdf

295-kolnp-2003-granted-form 5.pdf

295-kolnp-2003-granted-gpa.pdf

295-kolnp-2003-granted-reply to examination report.pdf

295-kolnp-2003-granted-specification.pdf

295-kolnp-2003-granted-translated copy of priority document.pdf

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Patent Number

225439

Indian Patent Application Number

295/KOLNP/2003

PG Journal Number

46/2008

Publication Date

14-Nov-2008

Grant Date

12-Nov-2008

Date of Filing

10-Mar-2003

Name of Patentee

VERTEX PHARMACEUTICALS INCORPORATED

Applicant Address

PATENT DEPARTMENT, 130 WAVERLY STREET, CAMBRIDGE, MA 02139-4242

Inventors:

#	Inventor's Name	Inventor's Address
1	FORESTER CORNELIA	8 NANCY AVENUE, PELHAM, NH 03076
2	PIERCE ALBERT	123 ORCHARD STREET APARTMENT #36, SOMERVILLE, MA 02144
3	KAY DAVID	4 CHURCH PATH, PURTON, WILTSHIRE 02144
4	DAVIES ROBERT	65 ORIENT AVENUE, ARLINGTON MA 0274
5	BEBBINGTON DAVID	6, LINDEN CLOSE, NEWBURY, BERKSHIRE R6141QA
6	KNEGTEL RONALD	3 BATH COURT, BATH STREET, ABINGDOM, BATH AND, SOUTH EAST SOMERSET OX1 X1EE
7	WANNAMAKER MARION	375 HARVARD ROAD, STOW, MA 01775
8	LI PAN	15 MYSTIC VIEW TERRACE, ARLINGTON, MA 02474

PCT International Classification Number

C07D 403/12, 401/14

PCT International Application Number

PCT/US01/28940

PCT International Filing date

2001-09-14

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	60/286, 949	2001-04-27	U.S.A.
2	60/257,887	2000-12-21	U.S.A.
3	60/232,795	2000-09-15	U.S.A.