| Title of Invention | PYRROLE COMPOUND |
|---|---|
| Abstract | Novel pyrrazole compounds and their use as pharmaceutical agents, in particular their use as TGF-beta signal transduction inhibitors. The disclosed invention relates to compounds of the structure (I) wherein (1) is a four, five, or six membered saturated ring and X is C, O or S. |
| Full Text | FIELD OF THE INVENTION The present invention relates to pyrrole derivative compounds of formula I and their use as pharmaceutical agents, in particular their use as TCF-beta signal transduction inhibitors. BACKGROUND AND PRIOR ART The transforming growth factor-beta (TGF-Beta) ("TGF-β") polypeptides influence growth, differentiation, and gene expression in many cell types The first polypeptides of this family that was characterized, TGF- (β1, has two identical 112 amino a single amino acid subunits that are covalently linked. TGF- (β1 is a highly conserved protein with only a single amino acid difference distinguishing humans f rom mice. There are two other members of the TGF-|β gene family that are expressed in mammals. TGF- β2 is 71% homologous to TGF- (β1 (de Martin, et al. (1987) EMBO J. 6:3673-:i677), whereas TGF- (β3 is 80% homologous to TGF- (β1 (Derynck, et al. (1988) EMBO J 7::;737-3743). The structural characteristics of TGF- (β1 as determined by nuclear magnetic resonance. (Archer, et al. (1993) Biochemistry 32:1164- 1171) agree with the crystal structure of TGF- (32 (Daopin, et al. (1992) Science 257:369-374; Schlunegger and Grutter (1992) Nature 358:430-434) There are atleast three different extracellular TGF- (β receptors, Type I, II and III that are involved in the biological functions of TGF- β1, - β2, - (β3 (For reviews, see Derynck (1994) TIBS 19: 548-553 and Massague (1990) Ann. Rev. Cell Biol. 6:597-641) The Type I and Type II receptors are transmembrane se rine/threonine kinase which in the presence of TGF- P form aheteromeric signaling complex (Wrana, et al (1992) Cell 71: 1003-1014). The mechanism of activation of the beteromerie signaling complex at the cell surface has been elucidated (Wrana, et al. (1994) Nature 370:341-347). TGF- β first binds the type II receptor that is constitutively active :ransmembrane serine/ threonine kinase. The type 1 receptor is subsequently recruited into complex, phoshorylated at the GS domain and activated to phosphorylate downstrearr signaling components (e.g. Smad proteins) to initiate the intracellular signaling cascade. A constitutively active type I receptor (T204D mutant) has been shown to effectively transduce TGF- β responses, thus bypassing the requirement for TGF- P and the type II receptor (Wiese •, et al. (1995) EMBO J 14: 2199-2208). Although no signaling function has been discovered for the type III receptor, it does increase TGF-β2's affinity for the type II receptor making it essentially equipotent with TGF-β1 and TGF-β3 (Lopez-Casillas, et al. (1993) Cell 73: 1435-1444). Vascular endothelial cells lack the Type 111 receptor. Instead endothelial cells express a structurally related protein called endoglin (Cheifetz, et al. (1992) J. Biol. Chem. 267:19027-19530), which only binds TGF-β1 and TGF-β3 with high affinity. Thus, the relative potency of the TGF-β's reflects the type of receptors expressed in a cell and organ system. In addition to the regulation of the components in the multi-factorial signaling pathway, the distribution of the synthesis of TGF-β polypeptides also affects physiological function. The distribution of TGF-β2 and TGF-(β3 is more limited (Derynck, et al. (1988) EMBO J 7:3737-3743) than TGF-pl, e.g., TGF-p3 is limited to tissues of mesenchymal origin, whereas TGF-βl is present in both tissues of mesenchymal and epithelial origin. TGF-β1 is a multifunctional cytokine critical for tissue repair. High concentrations of TGF-βl are delivered to the site of injury by platelet granules (Assoian and Sporn (1986) J. Cell Biol. 102:1217-1223). TGF-βl initiates a series of events that promote healing including chemo taxis of cells such as leukocytes, monocytcs and fibroblasts, and regulation of growth factors: and cytokines involved in angiogenesis, cell division associated with tissue repair and inflammatory responses. TGF-βl also stimulates the synthesis of extracellular matrix components (Roberts, et al. (1986) Proc. Natl. Acad. Sci. USA 83:4167-4! 71; Sporn, et al. (1983) Science 219:1329-1330; Massague (1987) Cell 49:437-438) and most importantly for understanding the pathophysiology of TGF-βl, TGF-βl autoiregulates its own synthesis (Kim, et al. (1989) J. Biol. Chem. 264:7041-7045). SUMMARY OF THE INVENTION The disclosed invention relates to compounds of the structure: wherein is a four, five, or six membered saturated ring and X is C, O or S; Rl is unsubstituted or substituted phenyl; unsubstituted or substituted pyridine; unsubstituted or substituted pyridine N-oxide; unsubstituted or substituted quinoline; unsubstituted or substituted quinoline N-oxide; unsubstituted or substituted naphthyridine; unsubstituted or substituted pyrazine; fury I; unsubstituted or substituted thiazoly); unsubstituted or substituted imidazollyl; unsbustituted or substituted pyrazolyl; or unsbustituted or substituted thioplhenyl; wherein the substitution may be one or mere of the following: (Cl-C6)a1kyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (Cl-C6)lkoxy, (C2- C6)alkenyloxy, (C2-C6)alkynyloxy, (Cl-C6)a]kylthio, (Cl-C6)alkylsulphinyl, (Cl- C6)alkylsulphonyl, (Cl-C6)alkylamino, di-((Cl-C6)alkyl]amino, (Cl- C6)alkoxycarbonyl, N-(C1-C6)alkykarbamoyl, N,N-di-[(Cl-C6)lkyl)carbamoyl, (G2- C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino, N-(C1-C6)alkyl-(C2- C6)alkanoylamino, (C3-C6)alkenoyliamino, N-(C1 -C6)alkyl-(C3-C6)alkenoylamino, (C3- C6)alkynoylamino, N-(C1 -C6)alkyl (C3-C6)alkynoylamino, N-(C1-C6)alkylsulphamoyl, N,N-di-[(C 1 -C6)alkyl]sulphamoyl, (C1 -C6)alkanesulphonylamino, N-(C 1 -C6)a1kyl-(C 1 - C6)alkanesulphonylamino, carboxaraide, ethylene, thiophenyl, aminophenyl, trifluoromethyl, halo, trifluoromethoxy, hydroxymethyl, N-pyrrolidino, N-morphoIino, phenylthio, (Cl-C4)dialkylaminomethyl, methoxyphenyl, amino, hydroxy, carboxyl, phenyl, arylalky; R2 is unsubsthuted or substituted quinoline; unsbustituted or substituted quinoline N-oxide; unsbustituted or substituted phenyl; unsubstituted or substituted naphthalene; unsubstituted or substituted pyridine; unsubstituted or substituted pyridine N-oxide; unsbustituted or substituted quinazoline; unsubstituted or substituted cinnoline; unsubstituted or substituted benzodioxole; unsbustituted or substituted benzodioxane; unsubstituted or substituted pyrimidine; unsubstituted or substituted benzothiophene; or unsubstituted or substituted phenanthrolene; wherein the substitution may independently be one or more of the following: hydrogen, (Cl-C6)alkyl, (C2-C6)alkenyl, (C2- C6)alkynyl, (C1-C6) aHcylhalide, (Cl-C6)alkoxy, (C2-C6)alkenyloxy, (C2- C6)alkynyloxy, (Cl-C6)alkylthio, (CI-C6)alky)lsulphinyl, (Cl-C6)alkylsulphonyl, (Cl- C6)alkylamino, di-[(Cl-C6)alky))ammo, (Cl-C6)alkoxycarbonyl, N-(C1- C6)alkylcarbamoyl, N,N-di-[(C J-C6}alkyl]carbamoyl, aminooxy, N-(C1-C6)alkyl aminooxy, N,N-di-[(Cl-C6)alkyl]aminooxy, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino, N-(C1 -C6)alkyl-(C2-C6)alkanoylamino, (C3-C6)alkenoylamino, N-(C1-C6)alkyl-(C3-C6)alkenoylamiiio, (C3-C6)alkynoylamino, N-(C I -C6)alkyMC3- C6)alkynoylamino, sulphamoyl, N-(C1-C6)alkylsulphamoyl, N,N-di-[(Cl- C6)alkyl]sulphamoyl, (C1 -C6)alkanesulphonyla;mino, N-(C1 -C6)alkyl-(C1 - C6)alkanesulphonylamino, carboxami de, ethylene, phenyl, thiophenyl, aminophenyl, phenylthio, halo, cyano, pyridinyl, arylalkyl, hydroxy, N-pyrrolidino, N-morpholino, carboxyl, [5-phenyI-l,2,4-oxadiazole-3-yl]methoxy, 6-methyl-pyridazin-3-yloxy, (5-oxo- 2-pyrrolidinyl)methoxy, 2-(4,5-dihydro-lH-imidazolyl), N, N-dialkylcarbamoyloxy, 1- hydroxy-1-methylethyl, 4-fluorophenyl, 3,4-methylenedioxyphenyl, trifluoromethyl, trifluoromethoxy, wherein: X, is O, N, S, SO2.NR,3, C(O), or bond; Qi is hydrogen, phcnyl, 5-(2,2- difluoro-1,3-benzodioxolyI), C(O)Qs,, or pyridyl when m and n are independently 0-2, except when one is 0 the other cannot be 0; Qt is ORi i, NR|,R,2, halo, N-morpholino, N-piperazino-N'Ru, N-imidazolyl, H-pyrazolyl, N-triazolyl, N-(4-piperidinyIpiperidine), SO2R14, SORu, NHSO2R1S, acetamido, N-phthalimido, N-oxazolidino, N-imidazoIino, N- benzoxazolidino, N-pyrolidinonyl, N(N'-methylbenzimidazolino), N,N-di(Cl- C4)alkylamino(Cl-C4)alkoxy, N-beiizimidazolino; when m and n are independently 0-2, but one or the other of m or n is not 0; Q5 is hydroxy, methoxy, amino, diethylamino, dimcthylamino; Rio is hydrogen, halo, (Cl-C6)alkyl; Rn and R12 are independently hydrogen, (Cl-C6)alkyl, (Cl-C6)alkoxy, arylalkyl, (C3-C8)cycloalkyl, (C3- C8)cycloalkylmethyl, 4-(N-methyIpiperidiriylj, pyridyl, or Rt 1 and Rio can be taken together to form a 4,5,6, or 7 membered ring, or R| 1 and R12 can be taken together to form a 3,4, 5,6, or 7 membered ring; Rn is hydrogen, (Cl-C6)alkyl, 2-methoxyphenyl, 2-pyridimidinyl; Ru is 2-pyrimidinyl, N-methyl-2-imidazolyl, 4-chlorophenyl, 2- pyridylmethyl; R15 is (Cl-C6)alkyl, N-methyl-4-imidazolyl; Rt6 is hydrogen, halo, arylalkyl, aryl, wherein: Q2 is hydrogen, 4-imidazolyl, or C(O)NR24R25 when o and p are independently 0-2; Q2 is OR23, NR24R25, or N-morpholino, when o and p are independently 0-2, but one or the other of o or p is not 0; R20 is hydrogen, or (Cl -C6)alkyl; R2i is hydrogen, (Cl - C6)alkyl, or R2| and R20 can be taken together to form a 4,5,6, or 7 membered ring; R22 is hydrogen, (Cl-C6)alkyl, arylalkyl, aryl, or R2i and R22 can be taken together to be a 3, 4, 5, 6, 7 membered ring; R23 is hydrogen or (Cl-C6)alkyl; R24 is hydrogen, (Cl- C6)alkyl, or R24 and R25 can be takem together to form a 3,4, 5,6, or 7 membered ring, or R24 and R20 can be taken together to form a 6 or 7 membered ring; R25 is hydrogen, (Cl- C61alkvl. or acetvl. wherein: R30 is hydrogen, or (Cl-C6)alkyl; R31 is hydrogen, (Cl -C6)alkyl, 2-pyridyl, pyridylmethyl, amino, or hydroxy, or a group of the formula wherein: R32 and R33 are each independently hydrogen, (Cl-C6)alkyl, acetyl, (Cl- C4)aIkyIsuJphonyl, or R32 and R33 tan be taken together to form a 4, 5,6, or 7 membered ring, or a group of the formula wherein: X2 is CH2, O, or N; q is 2-3 except when Qj is a bond, q is 0-3; Q3 is NR36R37, or OR38, and R35 is hydrogen, or R,5 and Q3 can be taken together to form a 5 membered ring; R36, R37, and R38 are each independently hydrogen, or (Cl-C6)alkyl, or a group of the formula wherein: X3 is cyano, carboxamide, N,N-dimeihylcarboxamide, N,N- dimethyhhiocarboxamide, N,N-dimethylaminomethyl, 4-methylpiperazin-lyl-methyl or carboxylate, or a group of the formula wherein: Q6 is NR41R12; r is 2-3; R40 is hydrogen, or (Cl-C6)alkyl; R41 and R42are hydrogen, (CI-C6)alkyl, or R41 and R40 can be taken together to form a 6 or 7 membered ring. or a group of the formula wherein: Q7 is hydroxy, methoxy, diniethylamino, or N-piperidinyl; with the proviso that when one of Rl or R2 is tmsubtituted or substituted phenyl, then the other cannot be unsubstituted or substituted phenyl or thiophen-2-yl; and with the proviso that when R2 is quinolin-4-yl, substitution at the quinoline 7-position cannot include an aryl, heteroaryl, fused aryl, or fused heteroaryl; k is 1-8; R3 is one or more of the following: hydrogen; (Cl-C4)alkyl; (Cl- C4)alkylhydroxy; hydroxy; N,N-di(Cl-C4)alkylamino(CI-C4)alkoxy; benzyl oxymethyi; phenyloxymethyl; oxo; carboxyl; (C1-C4) alkylaryl; benzyloxy; acetoxy, amino(CI- C4)alkyl; (C2-C4)alkenyl; halo; O-(C1-C4)alkyl; chiorophenethyl; acetonitrile; unsubsituted or substituted phenyl; wherein the substitution may be one or more of the following: (Cl-C6)alkoxy, halo, carboxy, or (Cl-C6)alkoxycarbonyl; and the pharmaccutically acceptable salts, esters and prodrugs thereof. DETAILED DESCRIPTION OF THE INVENTION The term "effective amount" as used in "an effective amount of a compound of Formula 1," for example, refers to an amount of a compound of the present invention that is capable of inhibiting TGF beta. The general chemical terms used herein have their usual meanings. For example, as used herein, the teifn "C1-C4 alkyl", alone or in combination, denotes a straight-chain or branched-chain C1-C4 alkyl group consisting of carbon and hydrogen atoms, examples of which are methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, and the like. The term "geminal dimethyl" represents two methyl groups attached at the same substitution position. The term C3-C6 cycloalkyl" refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. The term 'spiro-fused C3-C6 cycloalkyl" refers to a C3-C6 cycloalkyl group as defined above tonded to a carbon atom through a spiro linkage. The term "C1-C4 alkoxy", alone or in combination, denotes an alkyl group as defined earlier, which is attached via an oxygen atom, such as, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, and the like. The term "C1-C4 alkylthio", alone or in combination, denotes an alkyl group as defined earlier and is attached via a sulfur atom, and includes methylthio, ethylthio, isobutylthio, and the like. As used herein, the term "halo" or "halogen" represents fluorine, chlorine, bromine, or iodine. The term "hydroxy," alone or in combination, represents an -OH moiety. The term "carboxy" or "carboxyl" refers to a carboxylic acid. The term "carboxamide" refers to a carbonyl substituted with an -NH2 moiety. The term "oxo" refers to a carbonyl group. As used herein, the term "heteroaryl" means an aryl moiety, which contains 1 -5 heteroaioms selected from O, S, and N. Examples of heteroaryl groups include pyrrolyl, pyrazolyl, pyranyl, thiopyranyl, furamyl, imidazolyl, pyridyl, thiazolyl, triaziny), phthalimidyl, indolyl, purinyl, and benzothiazolyl. As used herein, the term "aryl" represents a substituted or unsubstituted phenyl or naphthyl. Aryl may be optionally substituted with one or more groups independently selected from hydroxy, carboxy, C1-C6 alkoxy, C1-C6 alkyl, halogen, carboxamide, trifluoromethyl, hydroxymethyl, and hydroxy(C1-C4alkyl. The term "C3-Cg cycloalkyl" refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. The term "optionally substituted C3-C8 cycloalkyl" refers to a Cj-Cg cycloa Ikyl as defined herein unsubstituted or substituted with one or more groups independently selected from hydroxy, carboxy, Cu alkoxy, Ci-e alkyl, halogen, carboxamide, trifluoromethyl, hydroxymethyl, and hydroxy(C|-C4)alkyl. As used herein, the term "saturated heierocycle" is taken to be a 4-9 membered ring containing nitrogen and optionally one other atom selected from oxygen, nitrogen, and sulfur. The term "optionally substituted saturated heterocycle" is taken to be a saturated heterocycle as defined herein unsubstituted or substituted with one or more groups independently selected from hydroxy, carboxy, C14 alkoxy, Cj^ alkyl, halogen, carboxamide, trifluoromethyl, hydrcocymethyl, and hydroxy(CrC4)alkyl. As used herein, the term "C]~C6 alkyl" refers to straight or branched, monovalent, saturated aliphatic chains of I to 6 carbon atoms and includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, tsopentyl, and hexyl. The term "C]-C6 alkyl" includes within its definition the terms "C1-C4 alkyl" and "C|-Q» alkyl." "C\-C(, alkenyl" refers to a straight or branched, divalent, unsaturated aliphatic chain of 1 to 6 carbon atoms and includes, but is not limited to, methylenyl, ethylenyl, propylcnyl, isopropylenyl, butylenyl, isobutylenyl, /-butylenyl, pentylenyl, isopentylenyl, hexylenyl. "C]-C6 alkoxycarbonyl" represents a straight or branched d-Q alkoxy chain, as defined above, that is attached via the oxygen atom to a carbonyl moiety. Typical C]-Co alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, /-butoxycarbonyl and the like. The term "di(Ci-C6 alkyl)aniino" refers to a group of the formula: wherein each R group independently represents a "C1-C6 alkyl" group, as defined above. An "optionally substituted phenyl" is a phenyl ring that is unsubstituted or substituted with 1 to 5 substituents, more preferably 1 to 3 substituents, for example: halo, Ci-Cfi alkyl, C\-C(, alkoxy, Cj-C6 alkylamino, trifluoromethyl, nitro, and cyano. An "optionally substituted benzyl" is a benzyl ring that is unsubstituted or substituted with 1 to 5 substituents, more preferably I to 3 substituents, for example: halo, C i -C6 alkyl, Ci -C6 alkoxy, trifluoromethyl, nitro, and cyano. "Phenoxycarbonyl" refers to the group: phenyl-O-C(O>. "Aryl" refers to an unsaturated aromatic carbocyclic group of 6 to 14 carbon atoms having a single ring (e^., phenyl) or multiple condensed (fused) rings (e.g., naphthyl or anthracenyl). Unless otherwise constrained by the definition for the aryl substituent, such aryl groups can optionally be substituted with 1 to 5 substituents, more preferably 1 to 3 substituents, selected from the group consisting of halo, hydroxy, acetyl, nitro, cyano, Cj-C6 alkyl, C]-C6 alkoxy, phenyl, di(Cj-C6 alkyl)amino, trifluoromethyl, trifluoromethoxy, -S(O)m-(Ci-Q alkyl), and - S»(O)m-(phenyl), wherein m can be 0, 1, or 2. "Arylalkyl" refers to aryl groups attached to alkyl groups, preferably having 1 to 6 carbon atoms in the alkyl moiety and 6 to 10 carbon atoms in the aryl moiety. Such arylalkyl groups are exemplified by t>enzyl, phenethyl, and the like. Unless otherwise constrained by the. definition for arylalkyl, such arylalkyl groups can be optionally substituted with 1 w> 5 substituents, more preferably 1 to 3 substituents, selected from the group consisting of halo, hydroxy, nitro, cyano, C\-C(, alkyl, C]-C6 alkoxy, di(C]-C6 alkyl)amino, trifluoromethyl, trifluoromethoxy, carbamoyl, pyrrolidinyl, -S(O)m-(Ci-C6 alkyl), and-S(O)n,-(phenyl), wherein m can be 0,1, or 2. The arylalkyl groups may be optionally substituted on the aryl moiety, the alkyl moiety, or both the aryl moiety and the alkyl moiety. The term "heterocycle" represents an unsubstituted or substituted S- to 7- membered monocyclic, or 7- to 11-membercd bicyclic heterocyclic ring that is saturated or unsaturated and that consists of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen or sulfur, and including a bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring to another heterocycle as defined above. The term "heteroaryls" represents the above-defined heterocylic rings that are fused to a benzene ring to another lieterocylce as defined above. Unless otherwise constrained by the definition for the heterocyclic substituent, such heterocycles can be optionally substituted with I to 8 substituents selected from the group consisting of halo, nitro, cyano, hydroxy, acetyl, Cj-C6 alkyl, C1-Q5 alkoxy, C3-C10 cycloalkyl, optionally substituted phenyl, phenethyl, phenoxy, phenoxycarbonyl, optionally substituted benzyl, 1,1-diphenylmethyl, oxo, C\-C6 alkoxycarbonyl, (C]-Q> alkoxy)Ci-C6 alkyl-, trifluoromethyl, pyridyl, (pyrrolidinyl)Ci-C6 alkyl-, and (pyridyl)Ci-C6 alkyl-, di(Ci-C6 alkyl)amino, trifluoromethyl, trifluoromethoxy, -S(O)m- (C|-Cc, alkyl), and - S(O)m-(phenyI), wherein m can be 0,1, or 2. Examples of such heterocycles; include azepinyl, azetidinyl, benzazepinyl, benzimidazolyl, benzoazolyl, benzodioxolyl, benzodioxanyl, benzopyranyl, benzothiazolyl, benzothienyl, dihydropyrazolooxazinyl, dihydropyrazolooxazolyl, furyl, imidazolyl, imidazolinyl, imidazolidinyl, indolinyl, indolyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isoxazolidinyl, isoxazolyl, morpholinyl, napthyridinyl, oxadiazolyl, oxazolyl, oxazolidinyl phlhalimidyl, piperazinyl, piperidinyl, pyrazinyl, pyridyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrrolidinyl, pyrrolopyrazolyl, p>Trolyl, quinazolinyl, quinolinyl, quinuclidinyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiazolinyl, thiazolidinyl, thiadiazolyl, thienyl, thiomorpholinyl, triazolyl, and the like. Preferred heterocycles include: benzodioxolyU dihydropyrrolopyrazolyl, pyridyl, quinolinyl. Preferred embodiments of the invention include the following: One preferred embodiment of the invention are compounds of the structure: wherein is a five or six membered saturated ring; Rl is defined as in Claim 1; R2' is hydrogen; (Cl-C6)alkyl; (Cl-C6)a1kylthio; (Cl-C6)alkoxy; halo; thiophenyl; aminophenyl; N-pyrrolicilino; N-morpholino; R6' and R7' are independently one or more of the following: hydrogen, (Cl - C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynylf (C!l-C6)alkylhalide, (Cl-C6)alkoxy, (C2- C6)alkenyloxy, (C2-C6)alkynyloxy, (Cl-C6>lkyllhio, (Cl-C6)alkylsulphinyl, (Cl- C6)alky!sulphonyl, (Cl-C6)alkylamino, di-[(CI-C6)alkyl)amino, (Cl- C6)alkoxycarbonyl, N- C6)alkanoyl, (C2-C6)alkanoyloxy, (<:2-c6 n-> C6)alkanoylamino, (C3-C6)alkenoylamino, NHC1-C6)alkyl-(C3-C6)alkenoylamino, (C3- C6)alkynoylamino, N-(CI-C6)alkyl-(C3-C6)alkynoylamino, sulphamoyl, N-(C1- C6)alky!sulphamoy!,N,N-di-[(Cl-C6)alkyl}sulphamoyl,(Cl-C6)alkanesu]phonylamino, N-(C1-C6)alkyl-(C1-C6)alkanesulphonylarnino, carboxamide, ethylene, phenyl, thiophenyl, aminophenyl, phenylthio, halo, cyano, pyridinyl, arylalkyl, hydroxy, N-. pyrrolidino, N-morphoJino, carboxyl, [5-phenyl-l,2,4-oxadiazole-3-yl]methoxy, 6- methyl-pyridazin-3-yloxy, (5-oxo- 2-pyrrolidinyl)methoxy, 2-(4,5-dihydro-l H- imidazolyl), N, N-dialkylcarbamoyiloxy, ] -hydroxy-1-methylethyl, 4-fluorophenyl, 3,4- methyJenedioxyphenyt, trifluorometihyl, trifluoromethoxy, or a group of the formula wherein: X, is O, N, S, SO2.NR|3, C(O), or bond; Q, is hydrogen, phenyl, 5-(2,2- difluoro-1,3-benzodioxolyl), C(O)Qs or pyridyl when m and n are independently 0-2, except when one is 0 the other cannol be 0; Qi is ORJI, NR11R12, halo, N-morpholino, N-piperazino-N'Rn, N-imidazolyl, N-pyrazolyl, N-triazolyl, N-(4-piperidinylpipcridine), SO2Ru, SOR14, NHSO2R15, acetamido, N-phfhalimido, N-oxazolidino, N-imidazolino, N- benzoxazolidino, N-pyrolidinonyl, N(N'-methylbenzimidazolino), N,N-di(Cl- C4)alkylamino(Cl-C4)alkoxy, N-ben;timidazolino; when m and n are independently 0-2, but one or the other of m or n is not 0; Q5 is hydroxy, methoxy, amino, diethylamino, dimethylamino; R)0 is hydrogen, halo, (Cl-C6)alkyl; Ru and Rl2 are independently hydrogen, (Cl-C6)alkyl, (Cl-C6)alkoxy, arylalkyl, cycloalkyl, cycloalkylmethyl, 4-(N- methylpiperidinyl), pyridyl, or R1( and Rio can be taken together to form a 4, 5, 6, or 7 membered ring, or Ru and R)2 can be taken together to form a 3,4, 5, 6, or 7 membered ring; R13 is hydrogen, (Cl-C6)alkyl, 2 methoxyphenyl; Ru is 2-pyrimidinyl, N-methyl-2- imidazolyl, 4-chlorophenyl, 2-pyridylniethyl; R|- is (Cl-C6)alkyl, N-methyl-4- imidazolyl; R|6 is hydrogen, halo, arylalkyl, aryl, or a group of the formula * wherein: Q2 is hydrogen, 4-imidazolyl, or C(O)NR24R2s when o and p are independently 0-2; Q2 is OR.23, NR24R25, or N-moipholino, when o and p are independently 0-2, but one or the other of o or p is not 0; R* »s hydrogen, or (C1 -C6)alkyl; R21 is hydrogen, (Cl - C6)alkyl, or R21 and R20 can be takttn together to form a 4,5,6, or 7 membered ring; R22 is hydrogen, (Cl -C6)alkyl, arylalkyl, aryl, or R2i and R22 can be taken together to be a 3, 4, 5,6,7 membered ring; R« is hydrogen or (Cl-C6)alkyl; R24 is hydrogen, (Cl- C6)alkyl, or R24 and R2S can be taken together to form a 3,4,5,6, or 7 membered ring, or R24 and R2o can be taken together to form a 6 or 7 membered ring; R2S is hydrogen, (Cl - C6)alkyl, or acetyl, or a group of the formula wherein: R^o is hydrogen, or (Cl-C6)alkyl; RM is hydrogen, (Cl -C6)alkyl, 2-pyridyl, pyridylmethyl, amino, or hydroxy, or a group of the formula wherein: R32 and Rj3 are each independently hydrogen, (Cl-C6)alkyl, acetyl, alkylsulphonyl, or R32 and R33 can be taken together to form a 4,5,6, or 7 membered ring, * or a group of the formula wherein: X7 is CH2, O, or N; q is 2-3 except when Q3 is a bond, q is 0-3; Q3 is NR36R37, OR38, or a bond; R35 is hydrogen, 01 R35 and Q3 (when Q3 is a bond) can be taken together to form a 5 membered ring; R36, R37, and Rj8 are each independently hydrogen, or (Cl-C6)alkyl, or a group of the formula wherein: X3 is cyano, carboxamidc, N,N-dimethylcarboxamide, N,N- dimethylthiocarboxamide, N,N-dimethylaminomethyl, 4-methylpipera2in-lyl-methyl or carboxylate, or a group of the formula wherein: Qft is NR41R42; r is 2-3; R*, is hydrogen, or (Cl-C6)alkyl; R^ and R42 are hydrogen, (Cl -C6)alkyl, or R41 and R40 can be taken together to form a 6 or 7 membered ring, or a group of the formula wherein: Q7 is hydroxy, methoxy, or N-piperidinyl; k is 1-8; R3 is one or more of the following: hydrogen; (C1-C4) alkyl; (C1-C4) alkylhydroxy; hydroxy; N,N-di(Cl-C4)alkyIaimino(Cl-C4)alkoxy; benzyl oxymethyl; phenyloxymethyl; oxo; carboxyl; (C1-C4) alkylaryl; benzyloxy; acetoxy; amino(Cl- C4)alkyl; (C2-C4) alkenyl; halo; -O-(C1-C4) alkyl; chlorophcnethyl; acetonitrile; phenyl; or an optionally substituted phenyl; wherein the substitution may be one or more of the following: (C1 -C6)alkoxy, halo, cirboxy, or (Cl-C6)alkoxycarbonyl; with the proviso that R7' cannot be aryl; heteroaryl; fused aryl; or fused heteroaryl. and the pharmaceutically acceptable salts, esters and prodrugs thereof. Another preferred embodiment of the invention are compounds of the structure: wherein is a five or six membered ring; Rl is defined as in Claim 1; R3" is hydrogen; halo; trifluoromethyl; R4" is hydrogen; halo; (Cl-C6)alkyl; (Cl-C6)alkoxy; hydroxy; (Cl- C6)alkylsulphonyl; k and R3 are defined as in Claim I; and the pharmaceutically acceptable salts, esters and prodrugs thereof. Another preferred embodiment of the invention are compounds of the structure: » wherein is a five or six membered ring; R6 may be one or more of the following: hydrogen, (CJ-C6)alkyl, (C2- C6)alkenyl, (C2-C6)alkynyl, (C! -C6)alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (C1-C6)alkylthio, (Cl-C6)alkyIsulpWnyI, (Cl-C6)alkylsulphonyl, (Cl-C6)alkylamino, di-[(Cl-C6)alkyl]amino, (Cl-C6)all(oxycarbonyl, N-(C1-C6)alkylcarbamoyl, N,N-di- [(C1-C6)alkyl]carbamoyl, (C2-C6)alkanoy1, (C2-C6)alkanoyloxy, (C2- C6)alkanoylamino, N-(C1-C6)alkyt- C6)alkynoylamino, N-(C1-C6)a!kyhiuiphamoyl, N,N-di-{(Cl-C6)alkyl]sulphamoyl, (Cl- C6)a!kanesulphonylamino, N-(C1-C6)alkyl-(C1-C6)alkanesxriphonylamino, carboxamtde, ethylene, thiophenyl, aminophenyl, trifiuoromethy), halo, trifluoromcthoxy, hydroxymethyl.N-pyrrolidino, N-morpholino, phenylthio, dialkylaminomethyl, methoxyphenyl, amino, hydroxy, carboxyl, phenyl, arylalky; R2" is unsubstituted or substituted quinoIine-8-yl; unsubstituted or substituted quinoline-6-yl; unsubstituted or substituted 1-naphthyl; unsubstituted or substituted 2- naphthyl; unsubstituted or substituted 3,4-methylenedioxyphenyJ; unsbustituted or substituted 3,4-ethylenedioxyphenyl; unsubstituted or substituted benzothiophen-2-yl; wherein the substitution may indept ndently be one or more of the following: (C1 - C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6) alkylhalide, (Cl-C6)alkoxy, (C2- C6)alkenyloxy, (C2-C6)alkynyloxy, (C1-C6)alkylthio, (Cl-C6)alkylsulphinyl, (Cl- C6)alkylsulphonyl, (Cl-C6)alkylamino, di-[(Cl-C6)alkyl]amino, (Cl- C6)alkoxycarbonyl, N-(C1 -C6)alkylcarbamoyl, N ,N-di-[(C 1 -C6)alkyl]carbamoyl, aminooxy, N-(C1-C6)alkyl aminooxy , N,N-di-[(Cl-C6)alkyl)aminooxy, (C2- C6)alkanoyl, (C2-C6)a1kanoyloxy) (C2-C6)alkanoylamino, N-(C1-C6)alky!-(C2- C6)alkanoylamino, (C3-C6)alkenoylamino, N-(CJ -C6)alkyl-(C3-C6)alkenoylamino, (C3- C6)alkynoylamino, N-(C1-C6)alkyl-(C3-C6)alkynoylamino, sulphamoyl, N-(C1- C6)alkylsulphamoyl, N,N-di-[(Cl C6)alkyl]sulphamoyl, (Cl -C6)alkanesulphonylamino, N-(CI-C6)alkyl-(C!-C6)alkanesulphonylamino, carboxamide, ethylene, phenyl, thiophenyl, aminophenyl, phenylthio, halo, cyano, pyridinyl, arylalkyl, hydroxy, N- pyrroJidino, N-roorphoJino, carboityl, [5-phenyl-l ,2,4-oxadiazole-3-yl]methoxy, 6- methyl-pyridazin-3-yloxy, (5-oxo-2-pyrroIidiny1)methoxy, 2-(4,5-ditiydro-l H- imidazolyl), N, N-dialkylcarbamcyloxy, 1 -hydroxy-1 -methylethyl, 4-fluorophenyl, 3,4- methylenedioxyphenyl, trifluoromethyl, trifluoromethoxy, or a group of the formula wherein: X( is O, N, S: SO2,NR|j, C(O), or bond; Qi is hydrogen, phenyl, 5-(2,2- difluoro-1,3-benzodioxolyl), C(O)Q$, or pyridyt when m and n are independently 0-2, except when one is 0 the other cannot be 0; Qi is ORn, NRuRi2, halo, N-morpholino, N-piperazino-N'Ru, N-imidazolyl, N-pyrazolyl, N-triazolyl, N-(4-piperidinylpiperidine), SOJRM, SORM, NHSO2R15, acctamido, N*phthalimido, N-oxazolidino, N-imidazolino, N- benzoxazolidino, N-pyrolidinonyl, N(N'-methylbenzimidazolino), N,N-di(Cl- C4)alkylamino(Cl-C4)alkoxy, N-btnzimidazolino; when m and n are independently 0-2, but one or the other of m or n is not 0; Q$ is hydroxy, methoxy, amino, diethylamino, dimethylamino; R,o is hydrogen, halo, (CJ-C6)alkyl; Ru and R)2 are independently hydrogen, (Cl-C6)alkyl, (Cl-C6)all:oxy, arylalkyl, cycloalkyl, cycioalkylmethyl, 4-(N- methylpiperidinyl), pyridyl, or Rn and Rio can be taken together to form a 4,5,6, or 7 membered ring, or Rn and Rt2 can foe taken together to form a 3,4, 5,6, or 7 membered ring; R(3 is hydrogen,*(Ci-C6)alkyl, 2-methoxyphenyl; Ru is 2-pyrimidinyl, N-methyl-2- imidazoly], 4-chloropheny], 2-pyridylmethyl; Ri5 is (Cl-C6)alkyl, N-methyl-4- imidazolyl; R)6 is hydrogen, halo, arylalkyl, atyl, or a group of the formula wherein: Q2 is hydrogen, 4-imidazolyl, or C(O)NR24R:>s when o and p are independently 0-2; Q2 is OR2.1, NR24R25, or N-morpholino, when 0 and p are independently 0-2, but one or the other of o or p is not 0; R2o is hydrogen, or (Cl-C6)alkyl; R21 is hydrogen, (Cl- C6)aJkyl, or R2] and R20 can be taken together to form a 4, 5,6, or 7 membered ring; R22 is hydrogen, (Cl-C6)alkyl, arylalkyl aryl, or R2i and R22 can be taken together to be a 3, 4,5,6, 7 membered ring; R2j is hydrogen or (Cl-C6)alkyl; R24 is hydrogen, (Cl- C6)alkyl, or RI4 and R25 can be taken together to form a 3,4, 5,6, or 7 membered ring, or R24 and R2o can be taken together to form a 6 or 7 membered ring; R2s is hydrogen, (Cl - C6>lkyl, or acetyl, or a group of the formula wherein: R30 is hydrogen, or (Cl-C6>lkyl; R3t is hydrogen, (Cl-C6)alkyl, 2-pyridyl, pyridylmelhyl, amino, or hydroxy, or a group of the formula i wherein: R32 and R33 are each independently hydrogen, (Cl-C6)alkyl, acetyl, alkylsulphonyl, or R32 and R33 can be taken together to form a 4,5,6, or 7 membered ring, or a group of the formula wherein: X2 is CH2,0, or N; q is 2-3 except when Q3 is a bond, q is 0-3; Q3 is NR.viR37, OR38, or a bond; R3S is hydrogen, or R35 and Q3 (when Q3 is a bond) can be taken ) together to form a 5 membered ring; R36, R37, and R38 are each independently hydrogen, or (Cl-C6)alkyl, or a group of the formula wherein: X3 is cyano,*carboxamide, N,N-dimethylcarboxarnide, N.TM- dimethylthiocarboxamide, N?N-di!Tieihylaminomethyl, 4-methylpiperazin-lyI-methy! or carboxylale, or a group of the formula ) wherein: Q6 is NR^Ru; r is 2-3, R40 is hydrogen, or (Cl-C6)alkyl; R4( and R42 are hydrogen, (C1 -C6)alkyl, or R41 and R40 can be taken together to form a 6 or 7 membered ring, S or a group of the formula wherein: Q? is hydroxy, methoxy, dimethylamino, or N-piperidinyl; 0 k is ) -8; R3 is hydrogen; and the pharmaceutically acceptable salts thereof. aaa) 4-[2-(3-Trifluoromeihoxy-phenyl>4,5,6>7-tetrahydfo-pyrazolo[l,5- a]pyridin-3-yl]-quinoline, bbb) 4-[2-(2-Fluoro-phenyl>4,5,6,7-tetrahydro-pyrazolo[l,5-a]pyridin-3-yl]- quinoline, ccc) 4-(2-Quinolin-2-y]-44,6,7-tetrahydro-pyrazolo[ 1,5-a)pyridin-3-yl)- quinoline, ddd) 4-[2-(l-Ethyl-pyridiu-2-yl)-4,5,6,7-tetrahydro-pyrazolo[ 1,5-a]pyridin-3- yl]-quinoline,' eee) 4-(2-Quino1in-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, ffi) 2-(3-Quinolin-4-yl-4,5,6,7-ietrahydro-pyrazolo[ 1,5-a]pyridin-2-yl)- [ 1,8]naphthyridine, Sgg) 4-[5-(4-Fluoro-phenyl)-2-pyriclin-2-yl-5,6-dihydro-4H-pyTrolo[ 1,2- b]pyrazol-3-y4J-quinoline, hhh) 4-(6-Hydroxymelhyl -2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo{ 1,2- b]pyrazol>3yl)-quino]ine, iii) 4-(3-Pyridin-2-yl-5,6-dihydiro-4H-pyrroJo[l,2-b]pyrazol-2-yl)-quinoline, jjj) 4-(4-Methyl-2-pyridin-2-yl-5»6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline, kkk) 4-(5-BenzyJ-2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[ 1,2-b)pyrazol-3-yl)- quinoline, 111) 4-(5-Phenethyl-2-pyridin-2-y»-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline, mmm) 4-(5-Phenyl-2-pyridin-2-yl-5,6-dihydro-4HpyiTob[ 1,2-b]pyrazol-3-yl)- quinoline, nnn) 4-[2-(3-Trifluoromcthylphenyli)-5,6-dihydro-4H-pyrTolo[ 1,2-b]pyrazol-3- y]]-quinoline, ooo) 4-[2-(4-Trifluoromethyl-phenj'l)-5T6-dihydro-4H-pyrrolo[ 1,2-b)pyrazol-3- yl]-quinolinc, ppp) 4-(2-Pheny)-5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazol-3-yl)-quinoline, qqq) 2-Chloro-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline, m)6,8-Dimethoxy-4-[2-(6-methyl-pyridin-2-y])-5,6-dihydro-4H- pyrrolo[ 1,2b]pyra2ol-3-yl]-quinoline, sss) 4-[2-(6-Bromo-pyridin-2-yl)-5,,6-dihydro-4H-pyrrolo[ 1 ,2-b]pyrazol-3-yl]- quinoline, ttt) 6,8-Dimethoxy-4-[2-pyridin -2-yl-5,6-dihydro-4H-pyrrolo[ 1,2b]pyra2ol-3-yJ]- quinoline, uuu) 3-(4-FJuorophenyl)-2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo(l,2-b]pyrazoJe, vvv) 3-(4-Methoxy-phenyl)-2-pyri^n-2-yl-5,6-dihydro-4H-pyiTolof 1,2- bjpyrazolc, www) 3-(4-Fluorophenyl)-2 (6-me!hylpyridin-2-yl)-5,6-dihydro-4H-pyrroJo[ 1,2- b]pyrazole, xxx) 3-(4-Methoxyphenyl) 2-(6-metbyJpyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazole, yyy) 4-(2-Thiophen-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yI)quinoline, zzz) 4-[2-(6-Propylpyridin- 2-yl)-5,6-dihydro-4H-pyrrolo|; 1,2-b]pyrazol-3-y]]- quinoline, aaaa) 4-[2-(6-Isopropylpyriclin-2-yl)-516-dihydro-4H-pyrrolo[l,2-b]pyrazol-3- yljquinoline, bbbb) 4-[2-(6-Ethy]-pyridin-2-yl)-5v6-dihydro-4H-pyrrolo[ 1,2-b]pyrazoI-3- yljquinoline, cccc) 4-[2-(6-Methyl-pyridin-2-yl)-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrazoI-3-yl]- quinoiine, dddd) 4-[2-(3-F]uorophenyl)-5,6-dihydro-4H-pyrrolo[],2-b]pyrazol-3-yl]- quinolinc, ecee) 4-[2- quinoline, ffff) 4-[2-(4-Fluoro-phenyJ) 5,6-dihydiro-4H-pyrrolo[ 1,2-b]pyrazoJ-3-yl]- quinoline, gggg) 4-[2-(3-Trifluoromeihoxy-phenyl)-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-ylJ-quinolinc, hhhh) 4-[2-(4-Chloro-pyridin-2-yl)-5,6-clihydro-4H-pyrrolo[l ,2-bJpyrazol-3-y!]- quinoline, iiii)4-(2-(4-Fluoro-3-trifluoromethyl-phemyl)-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yl]quinoline, jjyj)4-[2-(2-FIuoro-3-trifluoromethyl-pheiiiyl)-5,6-clihydro-4H-pyrrolo[l,2-b]-pyrazol- 3-yl]-quinoline, kkkk) 4-[5-(3-Methoxy-phcnyI)-2-pyridin-2-yl-5,6-dihydro-4H-pyrTolo[ 1 ,2- b]pyrazol-3-yl]-quinoline, Hll)4-[2-(4-FluoA>-3-trifluorom«thyl-pheny])-5-(3-meibx)xy-phenyl)-5,6-dihydro-4H- pyrrolo[l ,2-b]pyrazol-3-yl] -quinoline, mmmm) 4-(7-Chloro-quinolin-4-yl>3-(6-methylpyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazole, nnnn) 4-(7-Ethoxyquinolin-4-yl)-3-(6-meihylpyridin-2-yl)-5,6-dihydro-4H- pyrrolo[l ,2-b]pyrazole, oooo) 6-(3-Quinolin-4-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-2-yl)-pyridine- 2-carboxylic acid hydrochloride, pppp) 6,7-Difluoro-4-[2-(6 methyl-pyridin-2-yl>5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quino1ine, qqqq) 6,7-Dimethoxy-4-[2-(6-methy]-pyridin-2-y])-5,6-dihydro-4H-pyrrolo[1,2- b]pyrazol-3-yl]-quinoline, rrrr) 3-Benzo[ 1,3]dioxol- 5-yl-2-(6-methyl-pyridin-2-yl>5,6-dihydro-4H- pyrTolo[ 1,2-b]pyrazole, ssss) 6-(4-Fluoro-phenyI)-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof ] ,2-b]pyrazol-3-yl]-quinol ine, tttt)6-Benzo[ 1,3]dioxol-5-yl-4-[ 2-(6-methyl-pyridin-2-yI)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yJ]-quinolinc, uuuu) 4-[2-(6-Melhyl-pyridin-2-yI)-5,6-dihydro-4H-pyrrolo[1^-b]pyrazol-3-y]]- 6-thiophen-2-yl-quinoline, vvvv) 4-[2-(6-MethyI-pyridin-2-yI)-5,6-dihydro-4H-pyrTolo[l^-b]pyrazol-3-yl]- 6-phcny)-quinoline, wwww) 8-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl]- quinoline, xxxx) 3-Benzo[b]lhiophen-2-yl-2-(6-methyl-pyridin-2-yI)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazok, yyyy) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-p>Trolo[1,2-b]pyTazol-3-yl)-quinoline-6- carboxylic acid methyl ester, zzzz) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl]- quinoiine-6-carboxylic acid methyl ester, aaaaa) 4-[2-(6-Methyl-pyricliin-2-yl)-5 (6-dihydro-4H-pyTrolo[ 1,2-b]pyrazol-3-yl]- quinoline-7-carboxylic acid methyl ester, bbbbb) 4-[2-Pyridin-2-yl-5, carboxylic acid methyl ester, ccccc) 2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo[5,l-c]morpholine, ddddd) 2-Pyridin-2-yl-3-quiiolin-4-yl-pyrazolo[5,l-c]morpholin-4-one, eeeee) Dimethyl- {3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl)-quinolin-7-yloxy]-propyl}-amine, fTfTf) {3-[6-Methoxy-4-(2 pyridin-2yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3- yl)-quinolin-7-yloxy]-propyl}-dimethyl-amine, figg^g) Cyclopropylmethyl-propyl-{3-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolofl,2-b]pyrazol-3-yl) quinolin-7-yloxy]-propyl}-amine, hhhhh) Diethyl- {3-[4-(2-pyridin-2-yl- 5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-y!oxy]-propyl}-amine, iiiii) Ethyl-methyl-{3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yl)-quinolin-7-yloxy]-propyl}-amine, iijjj) 3-[4-(2-Pyridin-2-yl-5,6-dihydlro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinolin- 7-yloxyJ-propylamine, kkkkk) 7-[3-(4-Methyl-pip«razin-l-yl)-propoxy]-4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinoline, 11111) Benzyl-methyl-{3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2- b]pyrazol-3-yl)-quinolin-7- yloxy]-propyl} -amine, mmmmm) 7-(3-Piperidin-l-yl-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yri-quinoline, nnnnn) 4-(2-Pyridin-2-yl-5 6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-7-(3- pyrrolidin-1 -yl-propoxy)-quinoline, ooooo) 7-(3-Azepan-1 -yl-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quinoline, ppppp) 7-(3-lmidazol-1 -yl propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, qqqqq) 7-(3-Pyrazol-l -yl-|jropoxy>4-(2-pyridin-2-yl-5,6-dihydro-4H-pyTrolo[ 1,2- blpyrazoW-yO-quinoIine, rtrrr) I'-{3-[4-(2-Pyridiii.2-yl-5J6-dJhydro-4H-pyrrolo[l,2-b]pyrazol-3-yl> quinolin-7-y!oxy]-propyI}-ll,4']bipiperidinyl, sssss) Cyclojtoopyl-( 1 -mcthyl-piperidin-4-yt)- (3-{4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[l^-b]pyrazol-3-yl)-qui!K)lin-7-yloxy]-propyl}-amine, tint) 4-(2-Pyridin-2-yl- S,6-dihydiro-4H-pyrroio[ 1,2-b]pyrazoI-3-yl)-7-(3- [ ] ,2,3]triazol-l -yl-propoxy>quinollne, uuuuu) Dimethyl-(3- {4-[2-(6-inethyl-pyrid in-2-yl)-5,6-dihydro-4H-pynrolo[ 1,2- b]pyrazol-3-yl]-quinolin-7-yk>xy}-propyl)-amine, vvvvv) Dicthyl-(3- {4-[2-(6-mcthyJ-pyridin-2-y1)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinolin-7-y^oxy}-propyl)-amine, wwwww) Cyc]opr xxxxx) Ethyl-methyl-(3-{4-[2-(6-rnethy1-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3 yl]-quinolin-7-yloxy) -propyl)-amine, yyyyy) Dimelhyl-{2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[l,2-b]pyra2ol-3- yl)-quinolin-7-yJoxy]-e«hyl}-aminc> zzzzz) Diethyl-{2-[4-(; -pyiidin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-bJpyrazol-3-yl)- qu inolin-7-yIoxy]-ethyl} -amine, aaaaaa) 7-(2-Pipcridin-1 -yl-cthoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazo)-3-yl)-quino]ine, bbbbbb) Ethyl-methyl- {.!-{4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b)pyrazol- 3-yl)-quinolin-7-yloxy|cthy)}-amine, cccccc) 4-(2-Pyridin-2- /N5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-7-(2- pyrrolidin-1-yl-cthoxy>-quir»olJne, dddddd) 7-[2-(4-Methyl-piperazin-1-yI)-ethoxy]-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol- 3-y!)-quino1ine, eeeeec) Dimethyl- {3-[ I -oxy-4-(2 -pyrid in-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)- ffffff) 7-Methy)su]fany]-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yJ)-quinoline, gfigtJgg) 7-Ethylsulfanyl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyra2ol- 3-yl)-quinoline, hhhhhh) 6-McthyJsulfanyJ-4-( 2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol- 3-yl)-quinoline, iiiiii) 7-Benfylsulfanyl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yl)-quinoline, jjjjii) 3-[4-(2-Pyridin-2-yI-.4i,6-dihydro-4H-pyrrolo[l,2-b]pyra2ol-3-yl)-quinolin- 7-ylsulfanyl]-propan-1 -ol, kkkkkk) Dimethyl- {2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl)-quinoIin-7-ylsulfanyl]-ethy]}-amine, llllll) Dimethyl [6-(3-quinolin-4-yl-5,6-dihydro-4H-pyrrolo[l^-b]pyrazol-2-yl)- pyridin-2-yl-methyl]amine, mmmmmm) 7-(2-Propoxy-ethoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, nnnnnn) N,N-Dimethyl-N'-[4-( 2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[ 1,2- b]pyrazol-3-yl)-pyridin-2-yl]-ethane-1,2-diamine, oooooo) N,N-Dimethyl-N'-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyTTolo[l,2- b]pyrazol-3-yl)-pyridin-2-yl]-propane-1,3-diamine, pppppp) 3- {3-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yloxy3-propyl}-oxiizolidJn-2one, qqqqqq) l-{3-[4-(2-Pyridin-2->l-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-propyl}-im idazolidin-2-one, mTnr) 3- {3-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yloxyJ-propyl}-3H-benzooxazol-2-one, ssssss) Dimethyl-(2- {4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo{ 1,2- b]pyrazol-3-yl]-pyridin-2-ylsulfanyl}-ethyl-amine, ttittt) 4-(2-Pyridin-2-yl-5,6-clihydro-4H pyrrolo[ 1,2-b]pyrazol-3-yl)-2pyrroHdin- 1-yl-quinoline, uuuuuu) 2-Phenylsulfanyl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazol- 3-yl)-quinoline, vvvvvv) 2-Morpholin-4-yl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-yl)-quinoline, wwwwww) 2-Ethylsulfanyl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-yl)-quinoline, xxxxxx) Phenyl-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pynolo[],2-b]pyrazol-3-yl)- quinol in-2-yl]-amine, yyyyyy) 2-Meftoxy-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[l,2-b]pyrazol-3-yI)- quinoline, zzzzzz) 2-Ethoxy-4-(2-pyrid«n-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline, aaaaaaa) 4-[2-(6-Phenylsu1fanyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline, bbbbbbb) Pheny}-[6-(3-quinolin-4-yl-5,6~dihydro-4H-pyrrolo[l,2-b]pyrazol-2-yl)- pyridin-2-yl]-amine, ccccccc) 4- {2-[6-(4-Melhoxy- phenyl)-pyridin-2-y]]-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl}-quinolinc, ddddddd) 4-[2-(6-Phenyl-pyridin-2-yl)-5,6-dihydro-4H-pyiTolo[l,2-b)pyrazol-3-yl]- quinoline, eeeeeee) 4-[2-(6-Morpholin-4 -yl-pyridin-2-yl)-5,6-d ihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yI]-quinoline, ffffffl) 4-[2-(6-Pyrrolidin-l yl-pyridin-2-yl)-5,6-dihydro-4H-pyrro!o[1,2- b]pyrazol-3-yl]-quinoline, ggggggg) 4-[2-(6-Methoxy-pyi idin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl]-quinoline, hhhhhhh) 2-{3-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-propyl}-in5oindole-1,3-^ione, iiiiiii) 7-(3-Fluoro-propoxy)-4-(2-pyridin-2-yI-5,6-dihydro-4H-pyrrolo[],2- b]pyrazol-3-yl)-quinoline, jjjjjjj) 7-(3-Fluoro-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quinoline, kkkkkkk) 7-(3-Chloro-propoxy)-4-(2-pyTidin-2-yl-5,6-dihydro-4H-pyrroIo[ 1,2- b]pyrazol-3-yl)-quinoline, 11111)]) 7-(3-Chloro-propoxy)-6-methcocy-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline, mmmmmmm) 7-(3-Chloro-propoxyH-[2-(6-methyJ-pyridin-2-yl)-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-3 yl]-quino)ine, nnnnnnn) (1 -{3-[7-(2-Chloro-ethoxy)-quinolin-4-yl)-5,6-dihydro-4H-pyrroIo[ 1,2- b]pyrazol-2-yl}-propeny!)-methylene-amine, ooooooo) N,N-D^ethyl-2-[4-(2 pyridin-2yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yl)-quinoMn-7-yloxy]-acctamide, PPPPPPP) 7-[2-((2R)-1 -Methyl pyrrolidin-2-yl)-ethoxy]-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]p;yrazoI-3-y) )-quinolinc, qqqqqqq) Dimethyl- {4-[4-(2-p;yridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yJ)-pyridin-2-yloxy]-butyl}-iminc, mini) 1 -{3-[4-(2-Pyridtn-2 yl-5,6-dihydro-4H-pyrrolo(l,2-b]pyrazol-3-yl)- pyridin-2-yk»cy]-propyl}-pyrrolidin-2-one, sssssss) 7-( 1 -Methyl-piperidii-3-ylmethoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)- dihydro-4H-pyrrolo[ 1 ^-b]p>Tazol-3-yl)-quinoline, uuuuuuu) 4-[2-(6-Mcthyl-pyridin-2-yl):5,6-dihydro-4H-pyn-olo[ 1,2-b]pyrazol-3-yl]- 7-propoxy-quinolinc, wvvvvv) 4-{6-Benzyloxymethyl-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl]-C|uinol ine, wwwwwww) {4-[2-(6-Methiyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo( 1,2- b]pyrazol-3-yl]-quinolin-7-yloxy}-acetic acid methyl ester, xxxxxxx) 7-lsopropoxy-4-[2-(6 meihyl-p)Tidin-2-yl)-5,6-dihydro-4H-pyn-olo[ 1,2- b]pyrazol-3-yl]-quinoline, yyyyyyy) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl]- 7-(3-morpholin-4-yl-propoxy)-quinoline, zzzzzzz) 4-(6-Benzyloxymethyl-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-6-yl)-quinoline, aaaaaaaa) 7-Ben2yloxy-2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo[ 1,5-a]piperidine, bbbbbbbb)2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinolin- 7-yloxy]-acetamide, cccccccc) 7-(5-Phenyl-[l,2,4]oxadiazol-3-ylmethoxy)-4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, dddddddd) 7-(2,2-Difluoro-benzo[ 1,3]dioxol-5-ylmethoxy)-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]py razol-3-yl)-quino)ine, eeeeeeee) 7-[2-($S)-1 -Methyl-pyrrolidin-2-yI)-ethoxy]-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, fffiYTR) 5-[4-(2-Pyridin-2-yl-! ,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolin- 7-y1oxymethyl]-pyrrolidin-2-one, gggggggg) 4-(6-Phenoxymethyl-2-pyridin-2-yl-5,6-dihydro-4H-pyrTolo[ 1,2- b]pyrazol-3-yl)-quinoline, hhhhhhhh) 4-(6-Methylene-2-pyudin-2-yl-5,6-dihydro-4H-pyrrolo( 1 ^-bJpyrazol-3- yl)-quinoline, iiiiiiii) 3-(4-Fluoro-phenyl)-6-methyler»e-2- 4H-pyrrolo[ 1,2-b]pyrazole, jjjjjjjj) 7-(]-Methyl-piperidir-2-ylmethoxy)-4-(2-pyrJdin-2-yl-5,6-dihydro-4H- pyrrolo[l ,2-b)pyrazol-3-yl)-quinoline hydrochloride, kkkkkkkk) 7-[2-( 1-Methyl-pyiTolidin-2-yl)-ethoxy]-4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline hydrochloride, 11I11I11> 4-[2-(6-Methyl-1 -oxy-pyridin-2-yl)-5,6-dihydro-4H-pynrolo[ 1,2- b]pyrazol-3-yl]-quinoline 1-cxide, mmmmmmmm) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo(l,2- b]pyrazol-3-yl]-quinoline I-oxide, nnnnnnnn) 4-[2-(6-Methyl-1 -oxy-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b)pyrazol-3-yl]-quinoline, oooooooo)7-(3-Chloro-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-yl)-quinoline I -oxide, pppppppp) 7-Methanesulfonyl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyTTolo[ 1,2- b]pyrazol-3-yl)-quinoline, qqqqqqqq) 3-(4-Fluoro-phenyI)-2-(6-methyl-1 -oxy-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazole, rrrrrnT) 4-(Quinolin-N-1 -oxkle-4-yl)-3-(6-methylpyridin-2-yl)-5,6-dihydro-4H- pyrrolo[l,2-b] pyrazole, ssssssss) 6-Me1hanesulfonyl-4 (2-pyridiri-2-yi-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quinoline, tltttttt) 7-EthanesulfonyI-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[ 1,2-bJpyrazol- 3-yl)-quinoline, uuuuuuuu) 4-(2-PyVidin-2-yJ-5,6 dihydro-4H-pym>lo[l ,2-b]pyrazol-3-yl)-7-[3- (pyrimidine-2-sulfonyl)-propoxy]-quinoline, wwvwv) 7-[3-( 1 -Methyl-1 H-iimdazole-2-sulfonyl)-propoxy]-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyTazo\-3-y\)-qmno\ine, wwwwwwww) 7-[3-(4-Chloro-benzene!»ulfonyI)-propoxy]-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrro1o[ 1,2-b]pyrazol-3-yl)-quinoline, xxxxxxxx) 4-(2-Pyridin-2-yI-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-7-[3- (pyridin-2-ylmcthanesulfonyl)-propoxy]-quinoline, yyyyyyyy) 4-(2-Pyridin-2-yl-5,6 dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-y1)-7-[3- (pyridin-2-ylmethanesulfinyl)-propoxy]-quinoline, zzzzzzzz) 4-(Quinolin-l-N-oxide-4-yl)-3-(6-methylpyridin-2-yl-1 -N-oxide)-5,6- dihydro-4H-pyrrolo [ 1,2-b]p]/razole, aaaaaaaaa) 3- {4-[2-(6-Methyl-p> ridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyTazol-3- yl]-quinolin-7-yl}-acrylicacid methyl ester, bbbbbbbbb) 3- {4-[2-(6-Methylpyrdin-2-yl-5,6-dihydro-4H-pyrTolo[ 1,2- b]pyrazol-3-yl]quinolin-7-yl]! -1 -piperidiin-1 -yl-propenone, ccccccccc) 3- {4-[2-(6-Methyl-pyridin-2-yl>5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazol-3- yl]-quinolin-6-yl}-acrylicacid methyl ester, ddddddddd) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo{ 1,2- b]pyrazol-3-yl]-7-vinyl-quiiH>line, eeeeeeeee) 4-[2-(6-Benzyl-pyridtn-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazo1-3-yl]- quinoline, ffTfffm) 7-Benzyl-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline, eeeggggfig) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline-7-c arboxylic acid, hhhhhhhhh) 4-[2-(6-Methyl-pyridim-2-y])-5,6-dihydro-4H-pyrroJo[I^- b]pyrazol-3-yl]-quinoline-6-carboxylicacid, iiiiiiiii) 3-{4-[2-(6-MethyJ-pyridin-2->'l)-5,6-dihydro-4H-pyrrolo[l,2-blpyra2ol-3- yI]-quinolin-7-yl} -acrylic acid, Jiiijjjjj) 3" {4-[2-(6-Methyl-pyridin-2-yI)-5,6-dihydro-4H-pyrrolo[1,2-bJpyrazol-3- yl]-quinolin-7-yl}-propionicacid, kkkkkkkkk) ' 4-[2-(6-Methyl-pyridim-2-yl)-3-quinolin-4-yl-5,6-dihyd«)-4H- pyrrolo{ 1,2-b]pyrazol-5-yl] -benzoic acid, Illllllll) 4-(2-Pyridin-2-yl-5,i5-dihydro-4H-pyrrok>[ 1,2-b]pyrazol-3-yl)-^uinoline-7- carboxylic acid cyclopentylamide, mmrnmmrnmnirn)4-(2-Pyridiiv-2-yl-5,6-clihydro-4H-pyrrolo[l,2-b]pyrazoI-3-yl)- quinoline-7-carboxylic acid (2-moiphoHn-4-yl-ethyl)-amide, nnnnnnnnn) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrro1o[l,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid [2-(l H-imidazol-4-yl)-ethylJ-amide, ooooooooo) 4-(2-Pyridin-2-yl-5,6-«lihydro-4H-pyrrolo[l,2-b}pyrazol-3-yl)- quinoline-7-carboxyiic acid (2-methyiamino-elhyl)-amidc, ppppppppp) 4-(2-Pyridin-2-yI-5,6- qqqqqqqqq) 4-(2-Pyridin -2-yl-5,6- rrrrrmT) (4-Methyl-piperazin-l -yl)-[4H>pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quino1in-7-yl]-methanone, sssssssss) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- ttttttttt) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yJ)-quinolinc-7- carboxylic acid cyclopropylamide, uuuuuuuuu) 4-(2-Pyridin-2-yl-5,6-4lihydro-4H-pyrro1o( 1,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid (l-ethyl-|3ropyl)-amide, vvvvvvvvv) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid elhylamide, wwwwwwwww) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b}pyrazol-3-yl)- quinoline-7-carboxylic acict isobutyl-amide, xxxxxxxxx) 4-(2-Pyridin-:>-yl-5,6-dihydro-4H-pyrrolo[],2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid lert-butylamide, yyyyyyyyy) 4-(2-Pyridin-:Nyl-5,6HJihydro-4H-pym3lo[1,2-b]pyrazol-3-yl)- quinoline-7-carboxyIic acid i sopropylamide, zzzzzzzzz) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ ] ,2-b]pyrazol-3-yl)-quinoline-7- carboxylic acid propylamide, aaaaaaaaaa) «4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid (2-methyl-butyl)-amide, bbbbbbbbbb) 4-(2-Pyridin-:!-yl-5,6-dihydro-4H-pynrolo[l,2-b}pyrazol-3-yl)- quinoline-7-carboxylic acid ((2S)-2-methyl-butyl)-amide, cccccccccc) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrroIo[ 1,2-b]pyra2Ol-3-yl)- quinoline-7-carboxylic acid (2S)-sec-bulylamide, dddddddddd) 4-(2-P>Tidin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- qainoline-7-carboxylic acid (2R)-sec-butylamide, eeeeeeeeee) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid ((lR)-1,2-dimethyl-propyl)-amide, ffffffffff) 4-(2-Pyridin-2-yl-5,6 dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline-7- carboxylic acid (pyridin-4-ylmethyl)-arnide, gg86£86ggg) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrTolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid (pyridin-3-ylmethyl)-amide, hhhhhhhhhh) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazol-3-yl> quinoline-7-carboxylic acid (pyridin-2-ylmethyl)-amide, iiiiiiiiii) 6-(3-QuinoIin-4-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazoI-2-yl)-pyridine- 2-carboxylic acid amide, jjjjjjiijj) l-(4-Methyl-piperazin-l-yl)-2-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolin-7-yloxy]-ethanone, kkkkkkkkkk) N-(2-dimethylamino-ethy1)-2-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl)-quinolin-7-yloxy]-acetamide, 1111111111) N-(2-dimethylaminoH:ihyl)-N-methyl-2-[4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinolin-7-yloxy]-acetamide, mmmmmmmmmm) N,N-Dimethyl-3[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl)-quinolin-7-yloxy]-benzamide, nnnnnnnnnn) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yI)- quino)ine-7-carboxylic acid amide, oooooooooo) 4-(2-Pyridm-2-yI-5,6-dihydro-4H-pyrrolo[l,2-H]pyrazol-3-yl)- quinoline-7-carboxylicacid(2-dimethylamino-ethyl)-methyl-amide, pppppppppp) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo{ 1,2-H]pyrazol-3-yl)- quino]ine-7-carboxylicaci quinoline-7-carboxylic acid dimethylamide, nrrrrrrtr) 4-(2-Pyridin-2-yi-5,<:>-dihydro-4H-pyiTolo[ 1,2-H]pyrazoJ-3-yl)-quinoline- 7-carboxyIic acid methylamide, ssssssssss) 4-(2-PyTidin-2-yl-5,-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quino]ine-7- carboxylic acid pyridin-2-y) amide, tttttttttt) N-(2,2-Dimethylamii(K>-ethy0-N-methyl-3-{4-[2-(6-methyJ-pyridin-2-yl)- 5,6-dihydro-4H-pyiTolo[1,2-b]pyrazol- 3-y1)-quinolin-7-yl} -propionamide, uuumiuuuuu) 2-(6-Melhyl-f»yridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazoI- 3-yl]-quinoline-6-carboxyHc acid (2-dimethy)amino-ethyl)-amide, vvvvvvvvvv) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline-6-«arboxylicacid(3-dimethylamino-propyl)-amide, wwwwwwwwww) 4-{2-(t»-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrro}o[ ] ,2- b]pyrazol-3-yl]-quinoline-6H:arboxylicacid(2-morpholin-4-yl-ethyl)-amide, xxxxxxxxxx) 1 -[2-(Quinolin-4-yl)-1 -(6-methyJ-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl] quinoline-7-carboxylic acid N,N- dimethylaminoethylamide, yyyyyyyyyy) 4-[2-(6-Methylpyridin-2 -yl)-5,6-dihydro4H-pyrro]o( 1,2-b]pyrazol- 3-yl]quinoJine-7-carbox-y(ic acid (2-pijperidin-l-y)-ethyl)amide, zzzzzzzzzz) N-(2-Dimelhylamino-ethyl)-3-{4-[2-(6-methyl-pyridin-2-yl)-5,6- dihydro-4H-pyrrolo[1,2-b]pyiazol-3-y1]-quinolin-7-yl}-propionamide, aaaaaaaaaaa) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline-7-carboxylicacid (3-dimethylamino-propyl)-amide, bbbbbbbbbbb) 4-[2-(6-MeJhy]-pyridin-2-yl)-5,6-dihydro-4H-pyrro]o[I,2- b]pyrazol-3-yl]-quinoline-7-Ciirboxy1ic acid (3-pyrrolidin-l -yl-propyl)-amide, ccccccccccc) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyn-olo[l,2- b]pyrazol-3-yl]-quinoline-7-carboxylicacid (3-morpholin-4-yl-propyl)-amide, ddddddddddd) 3- {4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyiTolo[ 1,2- b]pyrazol-3-yl]-quinolin-7-yl}-propionamide, eeeeeeceeee) 4-(2-Pyridin-2- yl-5,6-dihydro-4H-pyrrolo{ 1,2-b]pyrazol-3-yl)- quinoline-6-cart)oxylic acid (2-dimethylamino-ethyl)-amide, fffffffiYfT) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline-6- carboxylk acid (2-morpholin-4-yI-ethyl)-amide, ggggggggggg) 4-(2-Pyridin-2- yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl> quinoline-6-carboxylic acid, hhhhhhhhhhh) 4-(2-Pyridin-2- yI-5,6-dihydro-4H-pyrrolo{ 1,2-b]pyrazol-3-yl)- quinoiine-6-carboxylic acid hydrazide, iiiiiiiiiii) 4-(2-Pyridin-2-yi-5,6- j.ijjiiiijjj) 4-(2-Pyridin-2-y1-5,6- kkkkkkkkkkk) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-6-carboxylic acid amide, 11111111)11) 4-(2-Pyridin-2-yl-5,6- mmmmmmmmmmm) 4-(2-Py ridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl)-quinoline-7-carboxylic acid hydrazide, nnnnnnnnnnn) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-- quinoline-7-carboxylic acid hydroxyamide, ooooooooooo) 4-(2-Pyridin-2- yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid (2-amino-ethyI)-amide, PPPPPPPPPPP) 4-(2-Pyridin-2- yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid (2-hydroxy-ethyl)-amide, qqqqqqqqqqq) 4-(2-P>Tidjn-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-sulfonic acid amide, inriiiini) 4-(2-Pyridin-2-yl-5,6-cl»ihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline-7- sulfonic acid methylamide, iiiiiiiiiiii) [4-(2-Pyridin-2-yl-5,6-dihydro-4iH-pyrrolo[1,2-b]pyrazol-3-yl)-quinolin-7- yl]-carbamic acid methyl ester, jjjjjjtijjjjj) [4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolin-7- yl]-carbamic acid 2-hydroxy-clhyl ester, kkkkkkkkkkkk) [4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yI)- quinolin-7-yl]-carbamic acid 2-methoxy-ethyl ester, IllllUlllll) 1,3-Bis-f4-(2-pyridin-:!-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yl]-urea, mmmmmmmmmmmm) Dimethyl-carbamiic acid 4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[l ,2-b]pyrazol-3-yl)-qiiinolin-7-yl ester, nnnnnnnnnnnn) 7-Bromo-2-isoj3ropyl-4-(2-pyridin-2-yI-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, oooooooooooo) 2- (4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinolin-6-yl)-propan-2-ol, pppppppppppp) 7-(3-Chloro-propylsulfanyl)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, qqqqqqqqqqqq) 7-Broino-4-(4- :hIoro-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quinoline, n 11 n 11111 r) 8-Chloro-4-(2-pyridin- 2-yI-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yI)- quinolin-7-ol, ssssssssssss) 8-Bromo-4-(2-|i)yridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol- 3-yl)-quinolin-7-ol, tttttttttttt) 3-(7-Bromo-quinolin^-yl)-2-pyiidin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-4-ol, uuuuuuuuuuuu) 7-Bromo-4-(4-iiiethoxy-2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, vvvvvvvvvvvv) [3-(7-Bromo-quinolin-4-yl)-2-pyridin-2-yl-5,6- wwwwwwwwwwww) 3-(7-Bromo-quinolin-4-yl)-2-pyridin-2-yl-5,6-dihydro- pyrrolo[ 1,2-b]pyrazol-4-one, xxxxxxxxxxxx) 3-[4-(2-Pyridir -2-yl-5,6-dihydro-4H-pyrrolo[ 1 ^-b]pyrazol-3-yl)- quinolin-7-yloxy]-benzamide yyyyyyyyyyyy) W,A^Dimethyl-3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[l,2- b]pyrazol-3-yl)-quinolin-7-j'loxy]-thiobenzamide, ZZZZZZ777777) Dimethyl-{3 [4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrroJo[ 1,2- b]pyrazol-3-yl)-quinolin-7-yloxy]-benzyl} -amine, aaaaaaaaaaaaa) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[i,2- b]pyrazol-3-yl]-1 H-quinolin-2-one, bbbbbbbbbbbbb)* 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yI)- quinolin-7-ol, ccccccccccccc) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazoI-3-yl]-quinolin-7-ol, ddddddddddddd) 6-Methoxy-4 (2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1J.- b]pyrazol-3-yI)-quinolin-7-ol, eeeeeeeeeeeee) 3- {4-[2-(6-M ethyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinolin-7-yI}-propionic acid methyl ester, ffffffflffiff) 4-(6-Methyl-2-pyridin-2-yl-5?6-dihydro-4H-pyrrolo[ 1 ^-bjpyrazol- 3-yl)-quinoline. gfiegegggggggg) 3- {4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2- b]pyrazol-3-yl]-quinolin-6-yl}-propionic acid methyl ester, hhhhhhhhhhhhh) 7-Amino-4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrTolo[l,2-b]pyrazol-3-yl]-(iuinoline, iiiiiiiiiiiii) N,N-Dimethyl-3-{4-|2-(6-methyl-pyridin-2-yl)-5,6-d!hydro-4H- pyrrolo[1,2-b]pyrazol-3-yl]-cjuinolin-7-yl}-propionamide, iiiijjjjjjjjj) N-{3-[4-(2-Pyridin-2 -yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yJoxy]-propyl}-acetamide, kkkkkkkkkkkkk) N-Acetyi-N- {4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl]-t|uinoIin-7-yl}-acetamide, 1111111 HillJ> 2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo[l,5-a]piperidin-7-ol, mmmmmmmmmmmmm)7-Aceioxy-2-pyridin-2-yl-3-quinolin-4-yl-pyrazolo[l,5- a]piperidine, nnnnnnnnnnnnn) Methyl-{3-[4(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-yl)-quinolin-7-yloxy]-propyl}-amine, ooooooooooooo) 7-(Pjperidin-4-yloxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline, PPPPPPPPPPPPP) 4-[2-(6-Methyl-pyridin-2-yJ)-5,6-dihydj^4H-pyrrolo[l,2- b]pyrazol-3-yl]-quinoline-7-carboxylic acid (2-amino-I,I-dimethyl-ethyl)-amide, qqqqqqqqqqqqq) {6-[3-(4-Fluciro-phenyl)-5,6-dihydro-4H-f)yrrolo[1,2-b]pyrazol-2- yl]-pyridin-2-yl} -methanoi, iinniiinrr) pyridin-2-yl]-methanol, sssssssssssss) 4-[2-{6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyn-olo[ 1,2- b]pyrazol-3 -yl ] -phenol, ttttttttttttt) 7-( 1 -MethyJ-pyrroIidin-3-ylmelhoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-i|uinoline, uuuuuuuuuuuuu) 7-( 1 -Methyl-jiiperidin-4-ylmeihoxy)-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]p>Tazol-3-yl)-quinoline, vvvvvvvvvvvvv) 4-[2-(6-Mefhyl-pyridin-2-yl)-5,6-dihydr©-4H-pyrrolo[ 1,2- b]pyrazol-3-y]]-quinoline-7-carboxylic acid(2-dimethylamino-l ,1 -dimethyl- ethyl)-amide, wwwwwwww^'wwww) (S)-[3-(4-Fluoro-phenyl)-2-(6-methyl-pyridin-2-yl)-5,6- dihydro-4H-pyrro!o[ 1,2-b]pyrazol-6-yl]-methanol, xxxxxxxxxxxxx) (^?)-[3-(4-Fluoro-phenyI)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-6-j'I}-methanol, yyyyyyyyyyyyy) (5)-[3-(4-FIuoro-phenyl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-6-)l]-acetonii:rile, 777.7777777777) (/?)-[3-(4-Fluoro-phenyl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-6-> !]-accionii:rilc, aaaaaaaaaaaaaa) 4-(3-Pyridin-2yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-2-yl)- quinoline, bbbbbbbbbbbbbb)4-(6-Pyridin-2 y]-2,3-dihydro-pyra2olo[5,l-b]oxazol-7-y])- quinoline, cccccccccccccc) 3-[4-(2-Pyridhi-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yl]-oxazolidin-2-o»oe, dddddddddddddd) 1 -[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyn-o]o[ 1,2b)pyrazol-3-yl)- quinoIin-7-yI]-imidazolidin-2-one, eeeeeeeeeeeeee) 4-(2-Pyridin-2-yl-5,6-diihydro-4H-pyrrolo[ 1,2-b]pyrazoI-3-yl)-7- (pyridin-4-yImethoxy)-quinoline, fffffffiffiffi) 4-(2-Pyridin-2-y]-5,6-dihydro-4H-pyrrolo[ 1,2-b}pyrazol-3-yl)-7-(3- pyridin-3-yl-propoxy)-quiiKi(line, gggggggggggggg) 7-(4,5-Dihydifo-1 H-imidazol-2-yl)-4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrro]o{ J ,2-b]pyrazol-3-yl)-quinoliine, hhhhhhhhhhhhhh)4-[5-(4-Fluor.o-phenyl>2-(6-methy]-pyridin-2-yl)-5,6-dihydro-4H- pyrrolofl ,2-b]pyrazol-3-yl]- iiiiiiiiiiiiii)4-[5-(4-Fluoro-pheny4)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-ylJ- jjjjjjjjjjiljjj) 2-Pyridin-2-yl-3-quwK>lin-4-yl-pyrazolo[5,1 -cjmorpholine, kkkkkkkkkkkkkk)4-[2-(6-Vinyl-pyridin-2-yl>5,e-dihydro-4H-pyrrotofl.2-b}pyrazol- 3-yl]-quinoline, lllllllllinil) 3-{4-[2-(6-Methyl-pjTidin-2-yl)-5,6-dihydro-4H-pyrro]o[ 1,2-b]pyrazol-3- yl]-quinolin-6-yl}-acrylic acid, mmmmmmmmmmmmmm) 7-(6-Mcthyl-pyridazin-3-yloxy)-4-(2-pyridin-2-yl- 5,6-dihydro-4H-pyrrolo[ 1,2-lajpyrazol- 3-yl)-quino] ine, nnnnnnnnnnnnnn) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-7-[4- (4-pyrimidin-2-yl-piperazin-1 -yl)-butoxyj-quino1ine, oooooooooooooo) 7- {3-[4-(2-Mt:thoxy-phcnyl)-piperazin-1 -yl]-propoxy} -4-(2- pyridin-2-yl-5,6-dihydro-4H- pyrrol^ 1,2-b]pyrazol-3-yl)-quinoIine, pppppppppppppp) Pyridin-2-yl- {3-[4-(2-pyTidin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quinolin-7-yloxy]-pKq3yl}-ainine, qqqqqqqqqqqqqq) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline-7-tarboxylic acid (2-dimethylamino-1 -methyl-ethyl)- amide, iiiniiiiinii) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoIine-7-carboxylic acid amide, ssssssssssssss) 4-(2-Pyridin-2-yI-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid (J-dimethyllamino-propyl)-amide, tttuttmtttt) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl]- quino)ine-7-carboxylic acid f2-dimethylamino-ethyl)-methyl-amide, uuuuuuuuuuuuuu)N,N-Dimeth>l-3-{4-[2-(6-methyl-pyridin-2-yl)-5,6-dJhydro-4H- pyrTolo[l,2-bJpyrazol-3-yl]-quinolin-7-yl}-acrylamide, vvvvvvvvvvvvvv) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yI)- quinoline 1-oxide, wwwwwwwwww«wwww)7-BenEyloxy-4-[2-(6-niethyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl]-quinoline, xxxxxxxxxxxxxx) 4-[2-(6-Chlor*>6-dihydro-4H-pyrrolo loro-pyridin-2-yl)-5 [ 1,2- b]pyrazol-3-yl]-quinoline, yyyyyyyyyyyyyy) 6-(3-Quinolin-4-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b)pyrazol-2- yl)pyridine-2-carboxylic acid methyl ester, zzzzzzzzzzzzzz) 4-(7-Chloroquinolin-4-yl)-3-(pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2 Dbjpyrazole, aaaaaaaaaaaaaaa) 4-(2-Furan-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline, bbbbbbbbbbbbbbb) 3-{4-[H6-Methyl-pyridin-2-yl)-5,6-dihydro-4H- pyiTolo[l,2-b]pyrazoI-3-yl]-C|uinolin-6-yl}-acrylic acid methyl ester, ccccccccccccccc) 4-[2-(2-Meth>l-thiazol-4-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline, ddddddddddddddd) 3-(4-Fluoro-phenyl)-2-(2-methyl-thiazol-4-yl)-5,6-dihydro- 4H-pyrrolo[ 1 t2-b]pyrazole, eeeeeeeeeeeeeee) 4-[2-(2-Meth> l-2H-pyrazol-3-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quinoline, fffffffffftlfTTT) 4-(2-Thiazol-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b)pyrazol-3-yI)- quinoline, eee&figgggggfiBSe) 4-[2-(l -Methyl- lH-imidazol-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl]-(|uinoline, hhhhhhhhhhhhhhh) 6,7-Dichloro-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl]- iiiiiiiiiiiiiii) (S)-6-Benzyloxymethyl-3-(4-fluoro-phenyl)-2-(6-methyl-pyridin- 2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazole, jjjjjjjjjjjjjjj) N,N-Dimethyl-3-{4-[2-(6-melhyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl]- quinolin-7-yl} -acrylamide, and the pharmaceutically acceptable salts, esters and prodrugs thereof. The compounds exemplied ;ibove are merely representative of the invention and are not limiting in any fashion. The compounds disclosed herein can be made according to the following schemes and examples. The examples should in no way be understood to be limiting in any way as to how the compounds may be mads. The skilled artisan will appreciate that the introduction of certain substituents will create asymmetry in the compounds of Formula (1). The present invention contemplates all enantiomers and mixtures of enantiomers, including racemates. It is preferred that the compounds of the invention containing chiral centers are single enantiomers. The compounds of the present invention can be prepared by a variety of procedures, some of which are illustrated in the Schemes below. It will be recognized by one of skill in the art that the individual steps in the following schemes may be varied to provide the compounds of Formula (I). The particular order of steps required to produce the compounds of Formula (I) is dependent upon the particular compound being synthesized, the starting compound, and the relative lability of the substituted moieties. The Compounds of Formula (1) may be prepared from several synthetic methods. In Scheme I, Methods A and B employ a cyclization of an appropriately substituted alkylideneamino-pyrrolidin-2-one (1), Method A, or an appropriately substituted alkanone-alkene-hydrazide (2), Method B. One skilled in the art would also appreciate Method C, a condensation of an appropriately substituted alkync (3) with a substituted synthon (4) to afford compounds of Formula (I). Step a depicts a cyclization of ai compound of formula (I) or a substituted compound of formula (2), where the R group($) can be any group(s), previously defined as said for Rl, R2 or R3 of Formula (I) from here on. Typically, the appropriate compound of formula (1) is contacted to a suitable base that can form the anion of the hydrazone, such as lithium diisopropylamide, potassium bis(trimethylsilyl)amide, lithium bis(trimcthylsilyl)amide, sodium bis(trimethylsilyl)amide, sodium hydride, lithium hydride, potassium hydride, sodium alkoxides (sodium hydoxide, sodium methoxide, or sodium ethoxide) or potassium alkoxides (potassium hydroxide, potassium methoxide, potassium t-butoxide or potassium ethoxide), with sodium hydride being the preferred base. The reaction is carried out in a suitable solvent, such as tetrahydrofuran, N,N- dimethyjformamide, dimethylsulfoxide or toluene, preferably N,N-dimethylformamide at temperatures of about 0 to 100 °C. The products can be isolated and purified by techniques well known in the art, such as precipitation, filtration, extraction, evaporation, trituration, chromatography, and recrystallization. Optionally, a variation of step b of Scheme I, may be appropriate for trie formation of 4,5,6,7-tetrahydro-pyrazolo[l,5- a]pyridine derivatives, when n equals to 2, to give the corresponding derivatives of Formula (I) as shown in Method B. Another variation a skilled artisan would appreciate is Method C for the formation of Formula (I), in Scheme I, is step b, which is known and appreciated in the art (Ranganathan, Darshan; Bamezai, Shakti, Tetrahedron Lett., 1983,1067-1070). For example, an alkyne of (3) is reacted with a compound of (4) in a suitable solvent, such as tetrahydrofuran, MN-dimethylformainide, or toluene, xylene, preferably xylene at temperatures of about 0 to 150 °C. The products can be isolated and purified by techniques described above. alkoxides (sodium methoxide, or sodium eihoxide) or potassium alkoxides (potassium methoxide, potassium t-butoxide or potassium ethoxide), with potassium bis(trimethylsilyl)amide being the preferred base. Generally, the reaction is carried out in suitable solvents, such as tetrahydrofuran and toluene or a combination of such, at temperatures of about -78 °C to ambient temperature. The product, formula (7), can be isolated and purified by techniques well known in the art, such as precipitation, filtration, extraction, evaporation, trituration, chromatography, and recrystallization. Another variation of the acylation step c, is to use a nitrile compound of formula (10) in place of the aromatic- or heteroaromatic-methyl compounds of formula (5). The product, formula (II), can be transformed to formula (7) by hydrolysis of the nitrile group and then subsequent decarboxylation. Generally, a compound of formula (I I) is dissolved in a hydrogen halide acid solution, preferably hydrogen chloride. The reaction is carried out at temperatures of about ambient to lefluxing for about 24 hours. Tins type of reaction is well known and appreciated in the art (Larock, R. C, Comprehensive Organic Transformations, copyright 1989, VCH, pp 993). Compounds of formula (10) can be acquired by treatment of an appropriate substituted aromatic- or heteroaromatic-methyl group with a halogenating reagent, such as N-halosuccinimides, preferably N- bromosuccinimide in carbon tetrachloride and subsequently reacting the aromatic- halomethyiene intermediate with a nitrile source, such as lithium cyanide, potassium cyanide, or trimethylsilyl cyanide, preferably sodium cyanide. The reaction is carried out at ambient temperatures for about 24 hours, as shown in step d, to afford the acetonitrile compounds of formula (10), (Larock, R. C, Comprehensive Organic Transformations, copyright 1989, VCH, pp 313; Eur. J. Org. Chem. 1999,2315-2321). In Scheme 11, step f, compound of formula (7) is contacted to an appropriate compound of formula (9), this type ol compound is known and appreciated in the art (Taylor, Edward C; Haley, Neil F.; Clemens, Robert J., J. Amer. Ckem. Soc, 1981, 7743- 7752), to give the compound of formula (1). Typically, the reaction is carried out in an acidic solvent, such as acetic acid and a suitable acid scavenger such as pyridine, or triethylamine. The reaction is carried out at temperatures of about 60 °C to ambient for 4-24 hours. The products can be isolated and purified by techniques described above. Another variation a skilled artisan would appreciate in the formation of Formula (I) is shown in Scheme 111. Scheme 111, step g, depicts n Claisen condensation of two appropriate substituted carbonyl esters, where X for both compounds of formula (6) and formula (13) is a suitable leaving group as previously described, preferably a CI-G6 alkoxy group. The Claisen condensation is well known and appreciated in the art (March, J., Advanced Organic Chemistry, copyright 1985, John Wiley and Sons, Inc., pp 437-439). The products of formula (14) can be isolated and purified by techniques described above. ]n Scheme IJJ, step f conditions can be applied to a compound of formula (14) with the appropriate compound of formula (9), to give the compound of formula (15). Typically, the reaction is carried out in a suitable solvent such as ethanol, N- methylpyrrolidinone or pyridine with pyridine being the preferred solvent. The reaction is carried out at temperatures of about 60 °C to ambient for 4-24 hours. The products can be isolated and purified by techniques described above. Step c, as described above, depicts the cyclization of a compound of formula (15) to give an optionally substituted compound of formula (16). Typically, the appropriate compound of formula (15) is reacted with to a suitable base that can form the anion of the hydrazone, sodium hydride being the preferred base in a suitable solvent preferably N,N- dimethylformamide at temperatures of about 0 to 100 °C. Optionally, a hydrolysis of the carboxyl ester of formula (16) can be performed. The products can be isolated and purified by techniques described above. Step h depicts the transformation of a carboxylic acid, formula (16), to a halide of formula (17). This transformation k well known and appreciated in the art (Larock, R. C, Comprehensive Organic Transformations, 2"d Ed., copyright 1999, John Wiley & Sons, pp 741-742). The halide of formula (17) can be used as a leaving group in combination with a substituted aryf- or heteroarylboronic acid or ester in the presence of a suitable palladium catalyst, preferably tetrakis(triphenylphosphine)palladium(0), and a suitable base such as potassium carbonate to further give compounds of Formula (I) > (Suzuki reaction see: Miryaura, N.; Yanagi, T.; Suzuki, A. The Palladium-Catalyzed Cross Coupling Reaction of Phenylboronic Acid with Haloarenes in the Presence of Bases. Synth. Commun., 1981, 513-518). Scheme IV, step j, depicts a carbonylation reaction for the formation of compounds of formula (6) and (20), where X is a suitable leaving group described as above, preferably a halogen. Compounds of formula (18) and (19) are used in the i formation of formula (6) and (20), respectively. The carbonyl group of formula (6) and (20) can further undergo a synthetic i ransformation to incorporate the leaving group X, where X is previously described. The Y group can be an aromatic or heteroaromatic halide and the reaction can be carried out in the presence of carbon monoxide, a suitable nucleophile, such as an amine or an itlcohol, with a palladium (0) or palladium (II) > catalyst, such as l,l'-bis(diphenylphc«sphino) ferrocene]dichloropalladium(ll): dichloromethane, tetrakis(triphenylpi«sphine)-palladium(O), bis(triphenylphosphine)palladium (II) chloride or palladium(H) acetate, tetrakis(triphenylphosphine)palladium(0), tris-(benzylideneacetone)dipaHa bis(diphenylphosphino) feiTOcene]diehloropaHadium(ll):dichlorornethane. AFI reagents of the reagents are combined in a suitable solvent, typically terahydrofuran, tohiene or ethylene glycol dimethyl ether, stirred at temperatures of about 0 to 80 °C. AH products can be isolated and purified by techniques described above. > Scheme V depicts the conveision of optionally substituted heteroaryls to optionally substituted carboxylic acid derivatives. Reaction sequences of this type are well known and appreciated in the art (Fife, WilmerK., J. Org. Chem., J983,1375-1377). A representative example of these reactions are as follow. For example, in step k, an > optionally substituted pyridine compound of formula (21), where R is previously described as the substitutions for R1 or R2 of Formula (I), is treated with hydrogen peroxide in acetic acid, at reflux. Formula (23) is produced from the crude intermediate, formula (22), and results from the removal of the solvent in step k, the addition of a nitrile source, preferably trimethylsilyl cyanide along with a disubstituted carbamyl halide, such as dimethylcarbamyl chloride. The reaction is carried out at ambient temperatures for about 24 hours. All products can be isolated and purified by techniques described above. Scheme V, step e, the nitiile compounds of formula (23) are hydrolized by an acid to give the carboxylic acid of formula (24). Generally, a compound of formula (23) is dissolved in a hydrogen halide acid solution, preferably hydrogen chloride, The reaction is carried out at temperatures of about ambient to reflux for about 24 hours. This type of reaction is well known and appreciated in the art (Larock, R. C, Comprehensive Organic Transformations, copyright 1989, VCH, pp 993). Formula (24) can then be converted to the appropriate carbonyl leaving j;roup, where X is a suitable leaving group described as above as shown in step m. This conversion is well known and appreciated in the art (Larock, R. C, Comprehensive Organic Transformations, copyright 1989, VCH, pp 966). Alternatively, the carboxylic acid of formula (24) can be reduced to the corresponding alcohol by borane in tetrahydrofuran and then converted to a leaving group. Theses transformations arts well known and appreciated in the art (Larock, R. C, Comprehensive Organic Transformations, copyright 1989, VCH, pp 552 reduction; pp 335 conversion to leaving group). The desired products may be isolated and purified by techniques described above. Scheme VI, step o, depict! a hydrazination of formula (7) affording a hydrazone compound of formula (27). Typically the reaction is carried out with a suitable source of hydrazine, preferably anhydrous hydrazine in an acidic solution consisting of an alcohol, such as methanol, ethanol, or projranol, and a hydrogen halo acid, preferably hydrogen chloride, is used as the solvent. The product can be isolated and purified by techniques described above. Compounds of formula (28) are commercially available or can be produced by a ring opening of appropriate substituted cyclic-carbonyl esters. Step p depicts these ring openings which can be accomplished by an acid hydrolysis using such as; hydrogen bromide with acetic acid or trimethyl aluminum can give the corresponding carboxylic acid derivatives to be further transformed to give compound of formula (28). Scheme VI, step c previously described, transforms the hydrazones of formula (27) to the hydrazides of formula (2), by acylation with compounds formula (28). The compound of formula (28) can be an appropriate carboxylic acid derivative, where X can be a leaving group previously described, preferably a halogen, most preferably a chloride, and where n and m can equal 1 or 2 carbons. The reaction is carried out in the presence of an acid scavenger such as pyridinc or triethylamine. The reagents are combined, and products isolated and purified by techniques described above. The conversion of amines to an amides by acylation is well known and appreciated in the art (Larock, R. C, Comprehensive Organic Transformations, copyright 1989, VCH, pp 979). One skilled in the art would appreciate the formation of formula (3) by the palladium-promoted coupling reaction of an alkyne and an aromatic halide. Such a reaction is known and appreciated in the art (Reisch, Johannes; Gunaherath, G. M. Kamal B.,J. Heterocycl. Chem., 1993; 1057-1060, Inouye, Masahiko; Miyake, Toshiyuki; Furusyo, Masaru; Nakazumi, Hiroyiiki, J. Amer. Chem. Soc, 1995; 12416-12425). For example, in Scheme VII, step q, an appropriate substituted alkyne of formula (29) and a variably substituted compound of formula (30), where R' and R" are previously described as substituions for Rl and R2 groups, respectively, for Formula (1) and where Y can be an appropriate leaving group such as a halide and the R group(s) can be one or more groups as previously described. Typically, the reaction is carried out by combining a compound of formula (30) with a palladium (0) or palladium (II) catalyst as described previously, preferably bis(triphcnylphosphine)palladium (II) chloride with a suitable base, such as trialkylamine or pyridine, preferably triethylamine along with a copper(l) halide to facilitate coupling to a compound of formula (29). All reagents are combined in a suitable solvent, typically terahydrofuran, toluene or ethylene glycol dimethyl ether, stirred at temperatures of about 0 to 80 °C. All products can be isolated and purified by techniques described above. Scheme VIII, depicts the incorporation of a heteroatom into the acyclic ring portion of Formula (I). In step r, an appropriate compound of formula (27) is reacted with an oxalic acid monoalkyl ester derivative, such as ethyl oxalyl chloride to give a compound of formula (31). Generally, the reaction is carried out in a suitable solvent, such as pyridine, at temperatures from ambient to reflux. The products can be isolated and purified by techniques described above. The reaction of step s, a compound of formula (31) is converted to a lactone of formula (32), by a sequence of reacti ons. An appropriate compound of formula (31) is dissolved in a suitable solvent, such as tetrahydrofuran, JV.W-dimethylformamide, or toluene, preferably W.Af-dimethylfonnamide at temperatures of about 0 to 80 °C. A suitable base, such as sodium carbonate, sodium bicarbonate, cesium carbonate, cesium bicarbonate, lithium carbonate, potassium carbonate, preferably cesium carbonate, is used in 1-3 molar equivalence, along with an appropriate alkylating reagent, such as a halo- alcohol, preferably 2-bromo-ethanol. The products can be isolated and purified by techniques described above. Step t depicts a ring opening and reduction of a compound of formula (32) to give a di-alcohol compound of formula (33). Typically, the reaction is carried out with a suitable reducing agent, such as boranes (sodium borohydride, borane-methyl sulfide complex or potassium borohydride), or aluminum hydrides (lithium aluminum hydride, sodium aluminum hydride or potassium aluminum hydride, preferably lithium aluminum hydride). All of the reagents are combined in a suitable solvent, typically dichloromethane, chloroform, tetiahydrorliran, dioxane, or diethyl ether and are stirred from 1 to 72 hours at a temperature of from ambient to about the refluxing temperature of the solvent. The desired product may be isolated and purified by techniques described above. The reaction »n step u depicts a ring formation of a compound of formula (33) to give a compound of formula (34), a compound derivative of Formula (I). The di-hydroxy compound of formula (33) is mixed with a suitable base, such as sodium hydride, potassium hydride, typically at approximately 2-4 molar equivalents of base per molar equivalent of the di-alcohol. A suitable sulfonylating agent, such as p-toluenesulfonyl chloride, p-nitro-benzenesulfonyl chloride, trifluoromethanesulfonic anhydride, or preferably methanesulfonyl chloride, is added in the reaction for the conversion of the hydroxy group of formula (33) into a suitable leaving group. The reaction is carried out in a suitable solvent, such as dichlo omethane, chloroform, tetrahydrofuran, dioxane, or diethyl ether, preferably tetrahydroluran, and stirred for 1 to 24 hours at a temperature of about 0 °C to ambient. The desired product may be isolated and purified by techniques described above. Scheme IX, elaborates substitution of the Rl and R2 groups of Formula (I). A representative transformation is seen m step v, a nucleophilic addition of appropriate compounds of formula (35) and (36), where Z is an halide, such as chloro, bromo, or iodo, or a sulfonic ester derivative substituted anywhere upon the aromatic ring, can undergo a nucleophilic substitution with appropriate nucleophiles, where the R group(s) is described above, to give compounds of formula (37) and (38), respectively. Typically, the reaction is carried out in the presence of C1-C6 alkoxide or variably substituted amine neat or in N.N-dimethylformamide, toluene or xylene, preferably MN-dimethylformamide at temperatures of about 100 °C to rellux. Alternatively, a metal-nucleophile, such as trialkylstannyls, or boranes with a suitable base such as, sodium alkoxides (sodium methoxide, or sodium ethoxide) or potassium alkoxides (potassium methoxide, or potassium ethoxide) can be used with a palladium catalyst, previously described, preferably tetrakis(triphenylphosphine) palladium(O). Or a skilled artisan can use as the metal-nucleophile a magnesium-halogen reagent (Grignard reagent) along with the palladium catalyst, to further elaborate the aryl-substituents at the C3 and C4 positions of the pyrazole of Formula (1). All reagents of the reagents are combined in a suitable solvent, typically tetrahydrofuran, toluene or ethylene glycol dimethyl ether, stirred at temperatures from room temperature to reflux. All products can be isolated and purified by techniques described above. Scheme X depicts the manipulation of hydroxy-aryi compounds of formula (40) for further alkylations and transformations to enable the scope of this invention, where the R group(s) are previously described. Representative conversions are shown in Scheme X. Step w, depicts the depiotection of a protected aromatic-hydroxy group of formula (39) to give a compound of formula (40), where the ~Pg** can be an alkoxide. The deprotection is well known aitd appreciated in the art (Greene T. W., Wuts, P. G. M. Protective Groups in Organic Synthesis, copyright 1991, John Wiley and Sons, Inc., pp 146-149). The product of fonrula (40) can be isolated and purified by techniques previous described. Step x, depicts the formation of an aryl ether compound of formula (40) to give the compounds of Formula (I). The formation of an aryl ether is well known and appreciated in the art (March, J., Advanced Organic Chemistry, copyright 1985, John Wiley and Sons, Inc., pp342-343, 5 89. and Mundy, B. P., Ellerd, M. G. Name Reactions and Reagents in Organic Synthesis, copyright 1988, John Wiley and Sons, Inc., pp 242, 530; Sawyer, J.S., Schmittling, E.A., Palkowiiz, J.A., Smith, 111, WJ., J. Org. Chcm., 1998, 63, 6338-6343). The products can be isolated and purified by techniques described above. Step y depicts an alkyation of a compound of formula (40) to give a variably substituted compound of formula (4 I), where the leaving group(s) "Lg" and "Lg"* can include such leaving groups, but are not limited to, halides, oxonium ions, alkyl perchlorates, ammonioalkanesulfonate esters, alky) fluorosulfonates, nonaflates, tresylates, triflates, and sulfonic esters, preferably the mesylate or tosylate, given "Lg" and "Lg'" are not the same group. Typically, the appropriate compound of formula (40) is reacted with a suitable base that can form the anion of the phenol, such as lithium carbonate, sodium carbonate, potassi jm carbonate, cesium carbonate, sodium hydride, lithium hydride, potassium hydride, with cesium carbonate being the preferred base, in the presence of a compound of formula (42). The reaction is carried out in a suitable solvent, such as tetrahydrofuran, N.N-dimethylformamide, dimethylsulfoxide, dimethyl acetamide or toluene, preferably N,N- dimethyl formamide at temperatures of about 0 to 100 °C. The products can be isolated and purified by techniques described above. Step z depicts the nucleophilic substitution of leaving group "Lg", by a nucleophile to form a compound of the formula (43). Nucleophilic substitution is well known and appreciated in the art (March, J., Advanced Organic Chemistry, copyright 1985, John Wiley and Sons, Inc., pp 255-446). Typically, the compound of formula (41) is reacted with a nucleophile of formula (44), which is typically, but not limited to, primary amines, secondary amines, alcohols or thiols. The reaction is carried out in a suitable solvent, such as tetrahydrofurin, N,N~di methyl formamide, dimethylsulfoxide, dimethyl acetamide or toluene, preferably A'.TV-dimethylformamide at temperatures of A skilled artisan would appreciate oxidation reactions on compounds of Formula (1) to further elaborate the scope of this invention. Representative examples are shown in Scheme XI. For example, a sulfur- or nitrogen-containing compound can be oxidized to an oxide (nitrogen or sulfur) or a bis oxide (sulfur) by oxidizing reagents. Typically, a compound of Formula (1) is contacted to an oxidant which is typically, but not limited to, hydrogen peroxide, acetoyl peroxide, benzoyl peroxide, tert-butyl peroxide, ozone, Oxone®, preferably Oxone®, in the presence of an acid which is typically, but not limited to, hydrochloric, sulfuric, nitric, phosphoric, acetic, trifluoroacetic acids, preferably acetic acid. The reaction is carried out in a suitable solvent, such as tetrahydrofuran, water, an alcohol, such as, but not limited to, ethanol, or methanol, preferably a mixture of water and tetrahydrofuran at temperatures of about 0 to 100 °C. Oxidations are well known and appreciated in the art (March, J., Advanced Organic Chemistry, copyright 1985, John Wiley and Sons, Inc., pp J089-1090). t A skilled artisan would appreciate palladium catalyzed couplings to elaborate the scope of the invention as shown in Scheme XII. Aryl substitutions of may be accomplished, through the use of a halo or sulfonyl leaving group, X, in combination with a substituted aryl- or heteroarylboronic acid or ester in the presence of a suitable palladium catalyst and a suitable base such as potassium carbonate as previously described in Scheme 111. Another palladium catalyzed reaction, incorporates alkenyl substitutions may be realized by reacting the corresponding aryl halide with an alkene in the presence of a suitable base such as triethylamine, a palladium catalyst, and a suitable ligand, such as triphenylphosphine. The resulting alkene may be reduced via hydrogenation to provide a substituted alkane-linked derivative (Heck reaction see: Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Advances in the Heck chemistry of aryl bromides and chlorides, Tetrahedron, 2001, 57(35), 7449-7476). A skilled artisan would also appreciate a carbonylation using an aromatic halide along with a palladium catalyst and an atmosphere of carbon monoxide in a suitable solvent such as methanol as previously described in Scheme IV. Scheme Xlll also elaborates compounds of Formula (I) to further enable the scope of this invention. A transformation of a benzylthio-aryl to a sulfonamide formation is depicted in step aa. A typical reaction is the treatment of a benzylthio-aryl with molecular chlorine in aqueous acetic acid solution and with the removal of the solvent then coupling the product to an appropriate substituted amine. One skilled in the art would also appreciate the conversion of an aryihalide of Formula (1) to the corresponding amine, shown in step bb. For example, the aryihalide is treated with benzophenone imine and a suitable base such as sodium methoxide, sodium wo-propoxide or preferably sodium /e/7-butoxide also using a palladium catalyst as previously described, preferably bis(dibenzylideneacetone)-palladium with an appropriate ligand such as 2,2*- bis(diphenylphosphino)-l,r-binaphthyl, this type of amination transformation is well known and appreciated in the art (Prashad, M.; Hu, B.; Lu, Y.; Draper, R.; Har, D.; Repic, O.; Blacklock, TJ.,J. Org. Chan., 2JI00,65,2612-1614). One skilled in the art would also appreciate other transformations of hetrocyclic substituions, as shown in Scheme XIV. Step cc, depicts a cyclizatioi of a hydroxyethyl-carbamic ester, to give an oxazolidinone. This type of cyclizi tion is well known in the art (Mistunobu, O., Synthesis, 1981, 1-28). Step dd, depicts a transformation of the aryl carboxylic ester, to a 4,5-dihydro-lH- imidazole by use of a Lewis acid such as trimethylaluminum. This type of transformation is well known in the an (Neef, G.; Eder, U.; Sauer, G.; J. Org. Chem., 1981,46,2824- 2826). Many of the compounds of the present invention are not only inhibitors of TGF- beta receptor kinase, but are also useful intermediates for the preparation of additional compounds of the present invention. For example, ester moieties may be reduced or hydrolized to the corresponding alcohols or carboxylic acid (Larock, R. C, Comprehensive Organic Transformations. Td Ed., copyright 1999, John Wiley & Sons, pp 1959-1968). These alcohols may then be activated and displaced by a number of nucleophiles to provide other compounds of the invention (see Larock, Comprehensive Organic Transformations, 2nd Ed., lohn Wiley & Sons, New York, pg. 779-780 (1999)). Additionally, in order to substitute alcohol derivatives with a corresponding amine, the skilled artisan would appreciate that necessary intermediates would incorporate certain appropriate leaving groups. Such leaving groups include, but are not limited to, halides, oxonium ions, alkyl perchlorates, ammonioalkanesulfonate esters, alkyl fluorosulfonates, nonaflates, tresylates, triflates, and sulfonic esters, preferably the mesylate or tosylate. Techniques lor the introduction of these groups are also well known to the skilled artisan; see, for example, March, Advanced Organic Chemistry, 5th Ed., John Wiley and Sons, New York, pg. 445-449 (2001). The skilled artisan will appreciate the secondary amine moiety can be reacted with an appropriate reagent to introduce a suitable amino protecting group "Pg", such as a formyl group, acetyl group, or preferably a tert-butoxycarbonyl moeity. These protecting groups may be removed at any convenient, point in the synthesis of the compounds of the present invention. Methods of formation and removal of an amino-protecting group are well known in the art; see, for example, Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley and Sons, New York, Chapter 7 (1999). For example, secondary amines may be acylated, alkylated or coupled with simple carboxylic acids or amino acids under standard conditions, in the presence of a peptide coupling reagent, optionally in the presence of a catalyst. Suitable peptide coupling reagents include N.JV'-carbonyldiiinidazolc (CDI), N,N'-dicyclohexylcarbodiimide (DCC), l-(3-dimethylarninopropyl)-3-cthylc:arbodiimide hydrochloride (EDC), and l-(3- (l-pyrrolidinyl)propyl)-3-ethylcarbodiimide (PEPC). Polymer supported forms of EDC (Tetrahedron Letters, 34(48), 7685 (1993)) and PEPC (U.S. Patent #5,792,763) have been described, and are very useful for the preparation of the compounds of the present invention. Suitable catalysts for tine coupling reaction include N,N-dimethy\-4- aminopyridine (DMAP). Such coupling reactions arc well known and appreciated in the art (Larock, R. C, Comprehensive. Organic Transformations, 2nd Ed., copyright 1999, John Wiley & Sons, pp 1941-1949). Also One skilled in the art would appreciate the treatment of a secondary amine with a phosgene reagent, with a suitable base such as pyridine and quenching the reaction with an amine or an alcohol to afford the appropriate ureas and carbamates of Formula (1) (March, J., Advanced Organic Chemistry, copyright 1985, John Wiley and Sons, Inc., pp 370-371). A skilled artisan would recognize several other transformations that can be applied to the synthetic process for production of useful and reactive intermediates. Such transformations include but are not limited to alkylation or acylations of the appropriate amine, O-alkylation of the hydroxy intermediates, or hydroxy-halogen exchange (Larock, Comprehensive Organic Transformations, 2nd Ed., John Wiley & Sons, New York, pg. 689-697(1999)). The skilled artisan will also appreciate that not all of the substituents in the compounds of Formula (I) will tolerate certain reaction conditions employed to i synthesize the compounds. These moieties may be introduced at a convenient point in the synthesis, or may be protected and i hen deprotected as necessary or desired. Furthermore, the skilled artisan wili appreciate that in many circumstances, the order in which moieties are introduced is not critical. The skilled artisan will appreciate that the compounds of Formula (1) in Methods ) A, B or C may be formed into acid addition salts using pharmaceutically acceptable acids. The formation of acid-addition salt!, is well known and appreciated in the art. The following preparations and examples further illustrate the preparation of compounds of the present invention and should not be interpreted in any way as to limit the scope. Those skilled in the art will recognize that various modifications may be made i while not departing from the spirit ind scope of the invention. All publications mentioned in the specification are indicative of the level of those skilled in the art to which this invention pertains. PREPARATION 1 » 4,5-Dihydroxy-pcntanoic acid ethyl ester A solution of ethyl pent-4-enoate (11.7 g, 91.3 mmol) in tetrahydrofuran (420 mL) and water (40 mL) is treated with csmium tetroxide (1.0 g, 4.2 mmol) and 4- methylmorpholine N-oxide (32.5 mL, 50% in water) at room temperature and stired for 3 > h, at which time no more starting material is detectable by TLC (SK>2, 2% methanol/dichloromethane, Rr=04Q). The mixture is concentrated in vacuo and the residue chromatographed on SiC>2 (2% methanol/ethyl acetate) to afford the title compound 14.37 g (96%) as a colorless oil. 'H NMR (CDCI3): 8 4.10 (q, J = 7 Hz, 2H), 3.60-3.80 (m, 2H), 3.45 (dd, J = 7,11 Hz, 1 1H), 3.00 (bs, 2H), 2.45 (dd, J = 1.3, 7 Hz, 2H), 1.70-1.85 (m, 2H), 1.25 (t, J = 7 Hz, 3H). washed with water and brine, dried over sodium sulfate, and filtered. The filtrate is concentrated in vacuo to provide ihe title compound, 4.0 g (80%), as a colorless liquid. 'H NMR (CDCb) 8 7.37-7.10 (m, 10H), 4.56 (s, 2H), 3.85-3.72 (m, 1H), 3.5-3.41 (m, 1H), 3.39-3.29 (m, 1H), 2.9-2.6 (m, 2H), 1.8-1.67 (m, 2H). PREPARATION 5 l-B«'nzyloxy-4-phenyl-butan-2-one To a solution of 1 -benzylo* y-4-phenyl-butan-2-oI, (8.4 g, 32.8 mmol) in dichloromethane (400 mL) is added a mixture of pyridinium chlorochromate (14.1 g, 65.6 mmol) with S1O2 (14 g) and stirred for 3 h at room temperature. The mixture is filtered through a pad of SiO2 and concentrated to provide the title compound 5.7 g (68%) as a colorless liquid. lH NMR (CDC13) 8 7.4-7.14 (m, 10H), 4.6 (s, 2H), 4.03 (s, 2H), 2.9- 2.82 (m, 2H), 2.8- 2.72 (m, 2H). PREPARATION 6 4-Acetoxy-3-phcnyl-bufyric acid methyl ester A mixture of 4-acetoxy-3-phenyl-but-2-enoic acid methyl ester, (1.0 g, 4.27 mmol), 10 wt. % palladium on activated carbon (1.0 g), acetic acid (10 mL) is shaken under an atmosphere of hydrogen on a Parr® Shaker. The mixture is filtered through a pad of Celite® and rinsed with methanol. The solution is concentrated in vacuo to yield 0.93 g (92%) of the title compound. 'H NMR (CDCI3) 8 7.40-7.10 (m, 5H), 4.30-4.05 (m, 2H), 3.60 (s, 3H), 3.55-3.40 (m, 1H), 2.80-2.50 (m, 2H), 2.10 (s, 3H). PREPARATION 7 Acetic acid 2-oxo-2-phenyl-ethyl ester A solution of 2-hydroxyaceto-phenone (JO g, 73.4 mmol), pyridine (17.4 g, 220.2 mmol), dichloromethane (734 mL), 3 crystals of 4-dimethylaminopyridine is cooled to - 78 °C. To this solution is added acetic anhydride (13.9 mL, 146.9 mmol) then wanned to room temperature and stirred for 18 h. The mixture is washed with water (200 mL) and brine (200 mL) then dried over sodium sulfate. The mixture is filtered and concentrated in vacuo to yield the title compound, 13 g (99%), as a colorless liquid. 'H NMR (CDCb) 5 7.9-7.2 (m, 5H), 5.32 (s, 2H), 2.20 (s, 3H). PREPARATION 8 4-(3-Methoxy-pheny|)-5//-furan-2-one 3-Methoxy-phenyl-boronic acid (2.16 g, 14.2 ramol) and trifluoromethansulfonic acid 5-oxo-2,5-dihydro-furan-3-yl ester1 (3 g, 12.92 mmol) in tetrahydrofuran (110 mL) is dissolved and de-gassed for 15 min. To this solution is added sodium carbonate (3.42 g, 32.3 mmol) in water (10 mL) and tetrakis-triphenylphosphine-palladium(O) (0.75 g, 0.646 mmol). The reaction mixture is refluxed for 45 min, cooled to room temperature, diluted with ether (50 mL) and filtered through a Celite® pad. The filtrate is washed with water and brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue is chromatographed on SiO2 (3:7 ethyl acetate/hexanes) to yield the title compound, 1.9 g (71%), as a white crystalline solid. 'H NMR (CDC13): 8 7.35 (m, 1H), 7.00-7.20 (itn, 3H), 6.30 (s, 1H), 5.2O(s, 2H), 3.80 (s, 3H). 1) Grigg, R.; Kennewell, P.; Savic, V. Tetrahedron, 1994, 5489-5494. PREPARATION 9 4-(4-Fluo«ro-phenyl)-5//-furan-2-one A method similar to PREPARATION 7, except employing 4-fluoro-phenyl- boronic acid, is used to yield the title compound as a white crystalline solid. 'H NMR (CDCb): 8 7.50-7.60 (m, 2H), 7.15-7.25 (m, 2H), 6.35 (s, 1H), 5.20 (s, 2H). PREPARATION 10 4-(3-Melhoxy-phenyl)-dihydro-furan-2-one To a solution of4-(3-methoxy-phenyl)-5//-furan-2-one, (1.9 g, 10 mmol) is tetrahydrofuran (100 mL) and is added Raney nickel (7.6 g, 50% suspension in water), the mixture is stirred under hydrogen (ambient pressure) 18 h at room temperature. The mixture is filtered through Celite® and concentrated in vacuo to yield the title compound, 1.54 g (80%), as a white crystalline sal id. 'H NMR (CDCh): 8 7.25 (m, 1H), 6.75-6.90 (m, 3H), 4.65 (dd, J = 7.9 Hz, J = 9 Hz, 1H), 4.25 (dd, J = 7.9. Hz, J = 9 Hz, 1H), 3.80 (s, 3H), 3.70-3.85(m, 1H), 2.90 (dd, 3 = 8.7, 17.5 Hz, 1H), 2.65 (dd, 1H, J = 8.7, 17.5 Hz). PREPARATION 11 4-(4-Fluoro-phenyl)-dihydro-furan-2-one A method similar lo PREPARATION 9, except employing 4-(4-fluoro-pheayl)- 5//-furan-2-one, (1.4 g, 7.86 mmol), i:s used to yield the title compound, 1.38 g (97.6%), as a white crystalline solid. 'H NMR (CDCl-i): 8 7.15-7.35 (m, 2H), 7.00-7.10 (m, 2H), 4.65 (dd, J = 7.8, 9 Hi, 1H), 4.20 (dd, J = 7.8, 9 Hz, 1H), 3.70-3.90 (m, IH), 2.90 (dd, J = 9,17.5 Hz, IH), 2.«Mdd, J = 9, 17.5 Hz, IH). f REPARATION 12 4-Bewyl-dihydio-furan-2-one A mixture of 3-benzoylpra|«onic acid (18 g, 101 mmol), potassium carbonate (10 g, 75 mmol), water (45 mL) and fitamaldehyde (36% in water, 7.8 mL, 101 mmol) is stirred at room temperature for 5 days, wanned to 30 °C and stirred for 3 additional days. To this mixture is added concentrated hydrochloric acid (10 mL) to pH 5.0, heated at 50 °C for 30 min. and copied to room temperature. The mixture is extracted with chloroform (4 x 200 mL) and the combined organic extracts washed with sodium carbonate (10% in water, 3 x 100 mL). The solution k dried with anhydrous sodium sulfate and filtered. The filtrate is concentrated in vacw to yield 4-benzoyl-dihydro-furan-2-one (12 g) as a colorless liquid. To a solution of 4-benzoyNlihydro-furan-2-one (5 g) in methanol (250 mL) in a Parr® reactor is added palladium dJoride (0.25 g). The mixture is shaken under hydrogen (50 PS1) for 3 h. The mixture is filtered through a pad of Celite® (40 g) and the filtrate concentrated. The residue is chromatographed on SiO? (10% ethyl acetate/hexanes, then 30% ethyl ace tate/hexanes) to yield the title compound, (2.5 g, 34% from 3-benzoylpropionic acid), as a colorless liquid. 'H NMR (CDC13) 57.40-7.05 (ra.5H), 4.38-4.30 (m, 1H), 4.02-3.98 (m, 1H), 2.98-2.70 (m, 2H), 2.68-2.55 (m, 1H), 2.38-2.25 (m, 1H). PREPARATION 13 4-Phem thyl-dihydro-furan-2-one A mixture of 3-benzyloxjB*ethyl-5-phenyl-pent-2-enoic acid methyl ester, (3.2 g, 13.5 mmol), 10 wt.% palladium on activated carbon (3.2 g), and acetic acid (40 mL) is placed in a Parr® Shaker under 1qpdrogen(45 PSI) and shaken 4 h. The mixture is filtered through a pad of Celite©and concentrated in vacuo. The residue is dissolved in toluene (30 mL), treated with /Hblunesulfonic acid (0.1 g), refluxed for 2 h and concentrated in vacuo. The reafce is chromatographed on SiC>2 (10% ethyl acetate/hexanes then 50% ethyl acetate/hexanes) to yield the title compound 1.2 g (62%) as a colorless liquid. 'H NMR (CDC13) 6 7.38-7.15 (i* f H), 4.50-4.40 (m, 1H), 4.00-3.92 (m, IH), 2.70-2.50 (m, 4H), 2.25-2.15 (m, 1H), 1 J»-l .80 (m, 2H). PREPARATION 14 4-Metlty|-dihydro-furan-2-one A method similar to PREPARATION 13, except employing 4-methy|-5H-furan-2- one (3 g, 30.6 mmol), is used to yield the title compound, 3.06 g (100%,) as a colorless liquid. 'H NMR (CDC13) 8 4.45-4.37 (m, 1H), 3.93-3.80 (m, 1H), 2.71-2.56 (m, 2H), 2.20-1.99 (m, 1H), 1.21-1.09 (m,3H). PREPARATION 15 4-Phenyl-dihydro-furan-2- 1,4-dioxane (29 mL) and sulfuric acid (29 mL)is stirred at room temperature for one hour then heated at 45 °C for 18 h. Volatile solvents are evaporated and the residue is extracted with toluene. The combined organic extracts are extracted with water and brine, filterd, and concentrated to yield the title compound, 2.2 g (71%), as a colorless liquid. 'H NMR (CDCI3) 6 7.38-7.1 (m, 5H), 4.73-4.65 (m, 1H), 4.3-4.22 (m,lH), 3,85-3.7 (m, 1H), 3.0-2.9 (m, 1H), 2.75-2.55 (m, IH). PREPARATION 16 (/?)-5-Benzylo:cymcthyl-dihydro-furan-2-one To a solution of (/?)-5-hydroxymethyl-dihydro-furan-2-one (5 g, 43.06 mmol) in tetrahydrofuran (130 mL) is added sodium hydride (2.58 g, 60% oil dispersion, 64.59 mmol) and tetrabutylammonium iodide (spatula) and stirred for 30 min. To the mixture is added benzyl bromide (6.18 mL, 51.67 mmol) and refluxed for 3 h. The mixture is cooled and diluted with ethyl acetate (150 mL), washed with a saturated solution of ammonium chloride (150 mL) and brine. The mixture is dried over magnesium sulfate, filtered and concentrated in vacuo to yield the title compound, 8.87 g (100%), as a pale yellow oil. 'H NMR (CDCI3): 8 7.25-7.40 (m, 5H), 4.63-4.72 (m, 1H), 4.56 (s, 2H), 3.68 (dd, J = 10.7, 4.0 Hz, 1H), 3.58 (dd, J = 10.7, 4.0 Hz, 1H), 2.04-2.68 (m, 4H). PREPARATION 17 (5>5-Benzyloxynwfhyl-dihydiro-fiiran-2-one A method similar to PREPARATION 16, except employing (S)-5-hydroxymethyl- dihydro-furan-2-one (4.0 g, 34 mtnol), is used to yieMthe title compound, 7.1 g (>98%), as a colorless oil. 'H NMR (CDCb): 5 7.25-7.40 (m, 5H), 4.63-4.72 (m, 1H), 4.56 (s, 2H), 3.68 (dd, J = 10.7,4.0 Hz, 1H), 3.58 (dd, J= 10-7.4.0 Hz, 1H), 2.04-2.68 (m, 4H). PREPARATION 18 4-(5-MeJhoxy-«etrahydro-ftiran-3-yl)-benzoic acid ethyl ester A solution of sodium nitrite (1.67 g, 24.2 mmol) in water (14 mL) is added dropwise to an ice cold mixture of «;thyl 4-aminobenzoate (4.0 g, 24.2 mmol) and tetrafluoroboric acid (7.8 mL, 48%, 59.78 mmol) and stirred for 30 min. Methanol (28.5 mL), 2,5-dihydrofuran (3.66 mL, 4K.4 mmol) and palladium(H) acetate (70 mg, 0.31 mmol) are added and the mixture re fluxed for 30 min. The mixture is filtered through Celite® pad and the filtrate diluted with dichloromethane (100 mL). The organic layer is separated and concentrated in vacuc. The residue is chromatographed on S1O2 (10% ethyl acetate/hexanes) to yield the title compound, 2.45 g (42%), as a white solid. 'H NMR (CDCI3): 8 7.98 (d, J = 8.3 Hz, 2H), 7.27-7.39 (m, 2H), 5.18 (m, 1H), 4.27-4.40 (m, 3H), 3.61 -3.87(m, 2H), 3.40(s, 3H),2.28-2.70 PREPARATION 19 4-(4-Chloro-ph<:nyl> A method similar to PREPARATION 18, except employing 4-chloroaniline (10.0 g, 78.4 mmol), is used to yield the title compound, 6.7 g (40%), as a pale yellow oil. 'H NMR (CDC13): 8 7.13-7.28 (m,4H), 5.14 (m, 1H), 4.14-4.31 (m, 1H), 3.54-3.82 (m, 2H), 3.32-3.41 (m, 3H), 2.28-2.63 (m, 1H), 1.87-2.08 (m, 1H). PREPARATION 20 4-(5-Oxo-lctrahydro-furan-3-yl)-benzoic acid ethyl ester To a solution of 75% 3-chloropcrbenzoic acid (2.7 g, 11.76 mmol) in dichloromethane (35 mL) is added magnesium sulfate (2.0 g, 16.6 mmol) and the mixture stirred for 30 min. Solids are removed by filtration and the filtrate treated with borontrifluoride etherate (0.5 mL, 3.92 mmol) and 4-(5-methoxy-tetrabydro-furan-3-yI)- benzoic acid ethyl ester (2.45 g, 9.8 mmol) in dkhloromethane (5 mL). The mixture is stirred at room temperature 18 h, diluted with ether (200 mL) and washed with a 10% solution of sodium thiosulfite (150 mL), a saturated solution of sodium bicarbonate (150 mL) and brine. The mixture is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is chromatogiaphed on SiO2 (elute with 20% ethyl acetate/hexanes) to yield the title compound, 2.2 g (96%), as an off-white solid. lH NMR (CDCI3): 8 8.04 (d, J - K.3 Hz, 2H), 7.31 (d, J = 8.3 Hz, 2H), 4.69 (dd, J = 9.0, 7.9 Hz, 1H), 4.26-4.42 (m, 3H), 3.82-3.95 (m, 1H), 2.96 (dd, J = 17.5, 8.7 Hz, 1H), 2.68 (dd, J = 17.5, 8.7 Hz, 1H), 1.39(1, J = 7.1 Hz,3H). PREPARATION 21 4-(4-Chlor»-phenyl) dihydro-furan-2-one A method similar to PREPARATION 20, except employing 4-(4-chloro-phenyl)- 2-methoxy-tetrahydro-furan (6.78 g, 32 mmol), is used to yield the title compound, 6.2 g (98%), as an off-white solid. 'H NMR (CDC13): 6 7.34 (d, J = 8 5 Hz, 2H), 7.17 (d, J = 8.5 Hz, 2H), 4.65 (dd, J = 9.1, 7.8 Hz, 1H), 4.23 (dd, J = 9.1, 7.8 Hz, 1H), 3.70-3.84 (m, 1H), 2.92 (dd, J = 17.5, 8.8 Hz, 1H), 2.63 (dd, J = 17.5, 8.8 Hz, 1H). PREPARATION 22 4-Hydroxy-3-(3-mefhoxy-plienyl)-butyric acid benzhydrylidene-hydrazidc Trimethylaluminum (12 ml-» 2 M in hcxane, 24 mmol) is added dropwise to a solution of benzophenone hydrazoiie (1.57 g, 8 mmol) in dichloromethane (20 mL) at room temperature and under nitrogen. After the mixture is stirred for 30 min, 4-(3- methoxy-phenyI)-dihydro-furan-2-one, (1.54 g, 8 mmol) in dichloromethane (5 mL) is added. The mixture is refluxed for 5 h cooled to room temperature and diluted with dichloromethane (30 mL). The mixture is treated with 4 N sodium hydroxide (30 mL) and stirred one hour. The organic layer is separated, washed with brine and, dried over magnesium sulfate. The mixture is filtered, concentrated in vacuo and chromatographed on SiO2 (2% methanol/dichloromclhane) to yield the title compound, 2.25 g (73%) as a pale yellow oil. 'H NMR (CDCI3): 5 8.35 (bs, 1H), 7.15-7.60 (m, 11H), 6.75-6.95 (m, 3H), 3.80-3.90 (m, 2H), 3.80 (s, 3H), 3.45-3.6 (m, 1H), 3.15-3.40 (m, 2H), 2.15 (m, 1H). PREPARATION 23 3-(4-Fluoro-phenyl)-4-hydroxy-butyric acid benzhydrylidene-hydrazide A method similar to PREPARATION 22, except employing 4-(4-fluoro-phenyi)- dihydro-furan-2-one (1.38 g, 7.67 mmol), is used to yield the title compound, 2.8 g (90%), as a white crystalline solid. 'H NMR (CDC13): 6 8.30 (bs, 1H), 7.15-7.60 (m, 12H), 6.95-7.15 (m, 2H), 3.75-3.95 (m, 2H), 3.40-3.60 (m, 1H), 3.20-3.35 (m, 3H). PREPARATION 24 5-(Aerr-Butyl-dimethyl-silylojy)-4-hydroxy-pcntanoic acid benzhydrylidcne- hydrazide A method similar to PREPARATION 22, except employing 5-(ie/7-butyl- dimethyl-silyloxy)-4-hydroxy-penta»noic acid ethyl ester (6.41 g, 23.2 mmol), is used to yield the title compound, 6.2 g (63%), as a yellow foam. 'H NMR (CDC13): 5 8.30 (bs, 1H), 7.20-7.60 (m, 10H), 3.65-3.85 (m, 2H), 3.50-3.60 (m, 1H), 3.00-3.10 (m, 2H), 2.80 (d, J = 4 Hz, 1H), 1.70-2.00 (m, 2H), 0.90 (s, 9H), 0.10 (s, 6H). PREPARATION 25 Methansulfonic acid 3-(benzhydrylidene-hydrazinocarbonyl)-2-(3-methoxy-phenyl)- p ropy I ester A solution of 4-hydroxy-3-(3-methoxy-phenyl)-butyric acid benzhydrylidene- hydrazide and (1.7 g, 4.38 mmol) and 4-dimethylaminopyridine (26 mg, 0.22 mmol) in pyridine (15 mL) is cooled to 0 °C treated with methanesulfonyl chloride (0.4 mL, 5.25 mmol) and stirred 18 h at room temperature. The mixture is diluted with dichloromethane (30 mL) and washed with 1 N hydrochloric acid (30 mL), a saturated solution of sodium bicarbonate and brine. The mixture: is dried over magnesium sulfate, filtered, concentrated in vacuo and chromatographed on SiO2 (2% methanol/dichloromethane) to yield the title compound, 1.64 g (80%), as yellow foam. 'H NMR (CDC1-0: S 8.35 (bs, 1H), 7.15-7.60 (m, 1 OH), 6.75-6.95 (m, 4H), 4.50 (m, 2H), 3.80 (m, 4H), 3.20-3.40 (m, 2H), 2.85 (s, 3H). PREPARATION 26 Methanesulfonic acid 3-(benzhydrylidenehydra/inurarbonyl)-2-(4-fluoro-phenyl)- prvpyl ester A method similar to PREPARATION 25, except employing 3-(4-fluoro-phenyl)- 4-hydroxy-butyric acid benzhydryl dene-fcydrazide (2.78 g, 7.4 mmol), is used to yield the title compound, 2.1 g (62%), as a yellow foam. *H NMR (CDC13): 5 8.30 (bs, 1H), 7.20-7.70 (m, J2H), 6.90-7.10 (m, 2H), 4.40-4.50 (m, 2H), 3.75 (m, 1H), 3.25-3.35 (m, 2H), 2.90 (s, 3Hfc PREPARATION 27 Mcthansulfonic acid 3-(benzhydiylid«ie-hydr«inocarbnyl)-l-(terr-butyl-dirnethyl- silykxymtfhy l)-pr*pyl ester A method similar to PREPARATION 25, except employing 5-(/ert-butyl- dimethyl-silyloxy)-4-hydroxy-pentsinoicacid benihydrylidene-hydrazide (5.55 g, 13 mmol), is used to yield the title compound, 6.08 g(93%), as a yellow foam. 'H NMR (CDCI3): 5 8.30 (bs, 1H), 7.50-7.60 (m,5H), 7.3O-7.40 (m, 5H), 4.80-4.90 (m, 1H), 3.70-3.80 (m, 2H), 3.00-3.15 (m, 5K), 2.00-2.20 (m, 2H), 0.90 (s, 9H), 0.10 (s, 6H). PREPARATION 28 1 -A mino-4-(3-raelhoKy-pheiiyl)-pyrro}idin-2-onc Concentrated hydrochloric acid (ft.35 mL) is added to a suspension of 1- (benzhydrylidene-amino)-4-(3-methoxy-|ihenyl)-pyrrolidiiii-2-one, (0.8 g, 2.16 mmol) in water (17 mL) and refluxcd for one hour. The mixture is concentrated in vacuo and water azeotroped away using ethanol and toluene. The residue is dissolved in methanol (5 mL) and loaded on SCX resin (5 g). The resin is washed with methanol and 2 M solution of ammonia in methanol. Appropriate fractions are concentrated to yield the title compound, 402 mg (92%), as a white crystalline solid. 'H NMR (CDC1,): 5 7.25 (t, J « 8 Hz, Mfc 6.75-6.85 (m, 3H), 4.20 (bs, 2H), 3.85 (m, IH), 3.80 (s, 3H), 3.45-3.60 (m, 2H), 2.80 (dd, J = 9,17 H2,1H), 2.50 (dd, J = 9,17 Hz, 1H). PREPARATION 38 J -Aminopyi rolidin-2- one hydrochloridc 4-Chlorobutyryl chloride(57 mL, 510 mmol)is added to a solution of benzophenone hydrazone (100 g, 510 mmol) and pyridine (41 mL, 510 mmol) in anhydrous dichloromethanc (520 mL) under nitrogen at a rate that maintains a gentle reflux throughout the addition. The mixture is stirred for 0.5 h and poured into water (1 L). The layers are separated and the organic layer washed with brine, dried (sodium sulfate), filtered, and concentrated in vacuo to yield 4-chloro-butyric acid benzhydrylidene-hydrazide as a residue. MS ES+m/e 303.1 (M+l). The residue is dissolved in tet rahydrofuran (1.5 L), cooled in an ice-water bath, treated with portions 60% sodium hydride suspended in mineral oil (20 g, 498 mmol) and stirred for 1 h. To the mixture is added saturated aqueous ammonium chloride solution (1 L) and ethyl acetate (1 L). The layers are separated and the organic solution washed with brine, dried (sodium sulfate), filtered ;ind concentrated in vacuo to yield 1- (benzhydrylideneamino)pyrrolidin-2-one as a residue. 'H NMR (CDCb): 8 7.58-7.62 (m, 2H), 7.39-7.46 (m, 4H), 7.29-7.36 (m, 4H) 3.31 (t, J = 7 Hz, 2H), 2.32 (t, J = 7 Hz, 2H), 1.91 (quintet, J = 7 Hz, 2H); MS ES+ m/e 267.1 (M+l). The residue is suspended in water (3 L), treated with concentrated hydrochloric acid (80 mL), and heated to reflux for 1.5 h. The solution is cooled to room temperature and extracted twice with dichloromethane. The aqueous portion is concentrated in vacuo followed by azeotropic removal of water with three portions of absolute ethanol and three portions of toluene to yield the title compound, 56 g (81%), as a white solid. 'H NMR (DMSO-d6): 8 3.58 (t, J = 7 Hz, 2H), 2.33 (t, J = 7Hz, 2H), 2.04 (quintet, J = 7 Hz, 2H), TOF MS ES+ exact mass calculated for C4H8N2 (p+1): m/z = 100.0637. Found: 100.0641. PREPARATION 39 (L)-N-Nitr A solution of 30 g L-prolinc, in in 100 mL water and 20 mL concentrated hydrochloric acid is cooled in ice bath and treated with 25 g sodium nitrite over 10 min. The mixture is stirred I h and concentrated in vacuo with minimal heat. The mixture is diluted with 1 N hydrochloric acid (100 mL) and extracted with chloroform (150 mL) and dichloromethane (2 x 200 mL). Organic portions are combined, dried (magnesium sulfate) and concentrated in vacuo. The residue was crystallized from dichloromethane- hexane to yield 5.58 g (L)-N-nitrsoproline. MS ES+ m/e 145 (M+l), MS ESm/e 143 (M-l). PREPARATION 40 3a JJ-pyrrolidino(],2-C] l,2,3-oxadiazolin-3-one (L)-N-Nitrsoproline (1.08 g, 7 mmol) is dissolved in ether (180 mL). This solution is added to trifluoroacetic anhydride (1.5 mL) cooled in an ice bath. The mixture is stirred 6 h in ice bath, evaporated with minimum heat, and chromatographed on SiC>2 (0 to 100 % ethyl acetate in hexane) to yield (0.75 g, 85%) of the title compound as an oil. MS ES+m/e 127 (M+l). PREPARATION 41 l-(Bcnzylidcnc-at«iino)-3-methyl-pyrrolidin-2-one To an ice-cooled solution of water (48 mL) and concentrated hydrochloric acid (20.4 mL) added, with stirring, a solution of sodium nitrite (16.5 g, 240 mmol) dissolved in water (48 mL) over 20 min. The sodium nitrite solution is added to a solution of 3- methypyrrolidinone (10.11 g, 102 mmol) in waiter (60 mL) over 30 min while cooling the reaction mixture in an ice-salt bath. The reaction mixture is stirred 3 h in an ice-salt bath and extracted with methylene chloride (2 x 300 mL). The organic layers are combined, dried (magnesium sulfate), and evaporated to yield 9.22 g, (71%) of the intermediate N- nitroso compound as an oil. Product formation is confirmed by TLC (5% methanol in PREPARATION 44 3-Benzyloxy-4-methoxy-phenylamine To a solution of 2-(benzyloxy>-]-methoxy-4-nitrobenzene (35.35 g, 136 mmol) in 1:1 ethyl acetate: ethanol (640 mL) at 80 °C is added tin(H) chloride hydrate in portions over 25 minutes. The mixture is heated at this temperature for 5 h. The mixture is allowed to cool to room temperature und stirred for 2 days. The mixture is poured into water (1 L) and neutralized with solid sodium bicarbonate. The mixture is extracted three times with ethyl acetate. The combined organic extracts are washed with water and brine, dried (sodium sulfate), filtered and evaporated to yield the title compound as a dark brown oil. MSES+m/e230(M+1). PREPARATION 45 2-Broifno-5-fluoropyridine This preparation is conducted in a manner similar to that described for the preparation of 2-bromopyridine from 2-aminopyridine in Org. Syn. Coll. Vol. 3, p. 136, except that 2-amino-5-fluoropyridine if used to yield the title compound, 47.5 g (55%), as a red oil. 'H NMR (CDC13) 5 7.3 (ddd, 1H), 7.5 (dd, 1H), 8.3 (d, 1H). PREPARATION 46 Elhyl 5-fluoropyridine-2-carboxylate A mixture of 2-bromo-5-fluoropyridine (5.00 g, 28.4 mmol), sodium acetate (9.33 g, 114 mmol), and 1-1 'bis(diphenylphospliino)ferrocene]dichloropalIadium(II):CH2Cl2 (0.464 g, 0.57 mmol) in ethanol (80 mL) in a F'arr® high pressure stainless steel reactor vessel is placed under an atmosphere of 50 psi carbon monoxide and heated at 80-100 °C for 4 h. The vessel is cooled, volatiles removed in vacuo, and the residue partitioned between ethyl acetate and water. The ethyl acetate exiract is washed with water and brine, dried over sodium sulfate, filtered, and evaporated to give a dark solid. The residue is chromatographed on SiO2 (10% ethyl acetate / hexanes) to yield the title compound 2.8 g (58%) as a white solid that is recrystallked from hexanes to give white crystals: mp 61-63 °C. PREPARATION 47 6-Methyl-pvridine-2-carboxylic acid methyl ester To a suspension of 6-metliyl-pvridine-2-carboxylic acid (10 g, 72.9 mmol) in methylene chloride (200 mL) cooled to 0 °C is added methano! (10 mL), 4- dimethylaminopyridine (11.6 g, 94.8 mmol), and EDC (18.2 g, 94.8 mmol). The mixture is stirred at room terr/perature for 6 h, washed with water and brine, and dried over sodium sulfate. The mixture is filtered and concentrated in vacuo. The residue is chromatographed on SiC>2 (50% ethyl acetatc/hexanes) to yield the title compound, 9.66 g (92%), as a colorless liquid. 'H NMR (CDCU) 6 7.93-7.88 (m, 1H), 7.75-7.7 (m, 1H), 7.35-7.3 (m, 1H), 4.00 (s, 3H), 2.60 (s, 3H). PREPARATION 48 6-Propy lpyridine-2-carboxylic acid A solution of 6-propyl-pyridine-2-carbonitrile (9.1 g, 61.9 mmol) in 6 N hydrochloric acid is heated at reflux for 18 h. The mixture is cooled to room temperature and concentrated in vacuo. The residue is partitioned between dichloromethaneand water. The aqueous portion is adjusted to pH 6 with saturated aqueous sodium bicarbonate solution and extracted five times with dichloromethane. The organic extracts are combined, dried (sodium sulfate), filtered, and concentrated in vacuo to yield the title compound, 8.32 g (81 %), as a white solid. TOF MS ES+ exact mass calculated for C9H12NO2 (p+l): m/z = 166.0868. Found: 166.0874. PREPARATION 49 6-]sopropylpyridinc-2-carboxylic acid A method similar to PREPARATION 48, except employing 6-isopropyl-pyridine- 2-carbonitrile (6.35 g, 43.4 mmol), is used to yield the title compound, 6.62 g (92%), as a white solid. TOF MS ES+ exact mass calculated for C9H)2NO2 (p+1): m/z • 166.0868. Found: 166.0867. PREPARATION SO 6-Ethylpyridine-2-carboxylic acid hydrochloride A method similar to PREPARATION 48 is used except employing 6-ethyl- pyridine-2-carbonitrile (7.94 g, 60.1 mmol) in 6 N hydrochloric acid (150 mL), heating at reflux for 18 h, cooling to room temperature, concentrating the mixture in vacuo, and co- evaporating with toluene four times to yield the title compound, 12.5 g (72%), as a white solid. TOF MS ES* exact mass calculated for C8Hl0NO2 (p+1): m/z = 152.0712. Found: 152.0701. PREPARATION 51 Methyl 3-fluorobenzoate A solution of 3-fluorobenzoic acid (3.0 g, 21.4 mmol) in methanol (71 mL) at 0 °C is treated drop wise with thionyl chloride (3.1 mL,42.8 mmol). The solution is stirred for 15 min at 0 °C, 2.5 h at room temperature, and 2 h at 50 °C. The reaction is concentrated in vacuo and the residue dissolved in ethyl acetate (150 mL). The organic solution is washed with saturated aqueous sodium bicarbonate (2 x 100 mL), brine (100 mL), and dried over sodium sulfate. The solution is decanted and concentrated to yield the title compound, 2.61 g (79%), a> a clear, colorless oil. 'H NMR (CDCI3): 5 7.85 (m, 1H), 7.75 (m, IH), 7.32 (m, 1H), 7.21 (m, 1H), 3.85 (s,3H). PREPARATION 66 Pyrazinc-2-cari)o«ylic acid methoxy-mcthyl-amidc To a solution of pyrazine-2-orboxylic acid (2.0 g, 16.1 mmol) in methylene chloride (54 mL) at 0 °C is added oxalyl chloride (7.1 mL, 80.6 mmol) and N,N~ dimethylformamide (0.12 mL, 1.6 mmol). The cooling bath is removed after 10 min and the reaction mixture stirred 18 h at room temperature. The reaction mixture is concentrated in vacua The residual oil is dissolved in methylene chloride (54 mL) and treated with iV,O-dimethylhydroxylar»iine hydrochloride (2.36 g, 24.15 mmol) and triethylamine (1J .2 mL, 80.6 mmol). The reaction mixture is stirred for 3 h at room temperature and diluted with methylene chloride. The resulting mixture is washed with water (50 mL), saturated aqueous bicarbonate (50 mL), and brine (100 mL), and concentrated in vacuo to yield the title compound, 2.35 g (88%), as a brown oil. 'H NMR (CDC13): 88.92 (s, 1H),8;.63 (s, 1H), 8.52 (s, 1H), 3.72 (s, 3H), 3.51 (s, 3H). MS (Cl, methane) m/e 168 (M+l). PREPARATION 69 3-Benzyloxymclhyl-5-phenyl-pont-2-enoic acid methyl ester Methyl (triphenylphosphoranylidiene)-acetate (1 eq)and 1-benzyloxy-4-phenyl- butan-2-one (I eq) are combined in toluene and refluxed for 18 h. Additional methyl (triphenylphosphoranylidiene)-acetate is added and refluxed for another 18 h. The solvent is removed in vacuo, and the residue suspended in hexanes and filtered. The filtrate is concentrated in vacuo to yield the title compound. 'H NMR (CDCb) 5 7.4-7.1 (m, 10H), 6.08 (s, 1H), 4.5 (s, 2H), 3.9 (s, 2H), 3.65 (s, 3H), 2.9-2.55 (m, 4H) PKEPARATION 71 (4-Fluoronaphlhalen-l-yl)acetonitriIc A solution of ]-chloromethyl-4-fluoronaphthalene (5.45 g, 5.66 mmol), sodium cyanide (333 mg, 6.79 mmol), and water (2 mL) in MN-dimethylformamide (30 mL) is stirred for 8 h, then heated at 70 °C for 15 h. The mixture is cooled to room temperature and partitioned between saturated sodium bicarbonate solution and ethyl acetate. The organic portion is washed with three portions of water, one portion of brine, dried (sodium sulfate), filtered and evaporated. The residue is chromatographed on S1O2 (30% ethyl acetate/ hexane) to yield the title compound, 4.67 g (90%), as a light brown solid. 'H NMR (CDCI3): 8 8.19 (d, J = 8 H;:, 1H), 787 (d, J = 8 Hz, 1H), 7.68 (ddd, J = 8, 7, 1 Hz, IH), 7.63 (ddd, J = 8, 7, 1 Hz, Ifcl), 7.51 (dd, J = 8, 5 Hz, 1H), 7.14 (dd, J = 10,8 Hz, lH),4.09(s, 2H). PREPARATION 73 Quinolin-6-yl-acctonirrile A solution of 6-meihyl-quinoline (3.00 g, 20.6 mmol), N-bromosuccinimide (3.96 g, 22.0 mmol), and benzoyl peroxide (0.51 g, 2.10 mmol) in carbon tctrachioride (100 mL) is stirred at reflux for 2 h. The reaction is cooled lo room temperature then washed with saturated aqueous sodium bisulfite (50 mL). The organic phase is passed through 30 g SiO2 (2 x) eluting with dichloromethane then diethyl ether. MW-Dimethylformamide (83 mL) is added to the combined organic fractions and solvent removed under reduced pressure leaving only the reaction mixture in WN-dimethylformamide. To the reaction mixture in A/.N-dimethylformamide is added sodium cyanide (1.22 g, 24.9 mmol) and potassium bicarbonate (2.51 g, 24.9 mmol). The reaction mixture is allowed to stir at 50 °C for 2 h. The cooled reaction mixture is poured into pH 7 buffer (75 mL) and extracted with ethyl acetate (2 x 100 mL). The organic layers are combined, washed with saturated aqueous sodium chloride (100 mL), dried over solid sodium chloride, and concentrated under reduced pressure to afford an oil that is purified by normal phase flash chromatography (120 g Biotage KP-Sil 40L: 10% ethyl acetate in hexanes for 5 min, 20% ethyl acetate in hexanes for 20 min, 40% ethyl acetate in hexanes for 20 min, 60% ethyl acetate in hexanes for 20 min, then 60-100% ethyl acetate in hexanes ramp over 20 min) to provids 645 mg (18%) of the title compound. MS ES+ m/e 169 (M+l). PREPARATION 77 2-Ethynyl-6-methyl-pyridine A solution of 2-bromo-6-methy1pyridine (0.5 g, 2.9 mmol) and (trimethylsilyi)acetylene (0.29 g, 2.9 mmol) in triethylamine (15 mL) is purged with argon. Copper(l) iodide (11 mg, 0.06 mmol) and (PPh^PdCh (42 mg, 0.06 mmol) are added and the reaction is stirred under argon at room temperature for 2 h. The solvent is removed in vacuo and the residue is diluted in ethyl acetate (50 mL) and water (50 mL). The organic is separated and washed with brine. The solvent is removed to afford a dark oil. This oil is diluted in methanol (50 mL) and treated with a 1 N sodium hydroxide solution (10 mL) and stirred for 3 h 3t room temperature. The aqueous is neutralized with 1 N hydrochloric acid and extracted with ethyl acetate. The solvent is removed in vacuo to afford a dark oil that is purified by SiOi column chromaiography to yield 1.16 g (24%) of the title compound as a light yellow oil. MSES+m/e 1I8(M+1). PREPARATION 78 (6-Methyl-pyi idin-2-yl)-propinoic acid ethyl ester A solution of 2-ethynyl-6rnethyl-pyridine (0.5 g, 4.3 mmol) in tetrahydrofuran (20 mL) is cooled to -78 °C and treated with 1.6 M N-butyllithium in hexanes (2.9 mL, 4.7 mmol) and stirred for 0.5 h. This solution is then treated with ethyl chloroformate (2.85 mL, 30 mmol) and stirred lor 3 h while the solution warms to room temperature. The reaction is quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The solvent is removed to yield 0.67 g (83%) of desired product as a light yellow oil. MSES+m/e 190 (M+l). PREPARATION 79 4-(2 (2-Pyridyl)ethynyl)quinoHne A mixture of triphenyphosphine oxide (5.56 g, 10 mmol) in 1,2-dichloroethane (30 mL) is cooled in an ice bath. Trifluoromcthanesulfonic anhydride (1.57 mL, 10 mmol) is added dropwise over 5 min. To this mixture is added a solution of l-(2- pyridyl)-2-(4-quinolyl)ethan-l-one(2.5 g, 10mmol)in 1,2-dichloroethane (lOmL) and triethylamine (2.84 mL, 20 mmol). The ice bath is removed and the mixture heated at reflux for 16 h. The mixture is diluted with dichloromethane (100 mL) and washed with water (3 x 100 mL), dried (magjiesium sulfate), filtered, concentrated in vacuo, and chromatographcd on SiO2 (0 to 100 % hexane in ethyl acetate) to yield 1 g of title compound as an oil. MSES+m/e231 (M+l). PREPARATION 80 4-Pyri(lin-2-ylethynyl~quinoline-2-carboxyIic acid «*hyl ester A mixture of ethyl 4-bromoquinoline-2-carboxylate (2.80 g, 10.0 mmol, J.Org. Chem. 1947,12, 456), triethylaminc (1.7 mL, 12 mmol), bis(triphenylphosphine)- palladium(Il)chloride (0.561 g, 0.80 mmol), Cul (0.114 g, 0.60 mmol), and 2- ethynylpyridine (1.11 g, 10.8 mmol) in CH3CN (80 mL) is heated at 75-80 °C for 18 h in a sealed tube. Additional triethylanwme (0.85 ml, 6.1 mmol), bis(triphenylphosphine)palladium (II) chloride (0.23 g, 0.40 mmol), and Cul (0.055 g, 0.29 mmol) is added and the mixture heated for an additional 18 h. The mixture is concentrated in vacuo and partitioned between water and chloroform. The chloroform extracts are washed with brine and evaporated. The residue is chromatographed on SiOj (50% ethyl acetate / hexanes) to yidid 1.52 g (50%) of a yellow soKd. Precipitation from ethyl acetate gave the title compound as yellow crystals: mp 129-131° C; MS ES+ m/e 303 (M+l). PREPARATION 81 3-Bcnifl-4-bromo-butyric acid A mixture of 4-benzyl-di!»ydrofuran-2-one (1.0 g, 5.6 mmol), acetic acid (1.7 mL), HBr (33% in acetic acid, 2.0 mL) is heated at 80 °C for 4 h. The mixture is cooled to room temperature, poured into kit-water (20 mL), and extracted with chloroform (2 x 30 mL). The combined organic exnacts are washed with water and brine, dried with anhydrous sodium sulfatc, filtered, Jaid concentrated in vacuo to yield 3-benzyl-4-bromo butyric acid, 1.5 g (99%), as a colorless liquid. 'H NMR (CDCI3) 5 7.30-7.12 (m, 50), 3.58-3.35 (m, 2H), 2.80-2.38 (m, 5H). PREPARATION 85 3-Benzyl-4-bromo-butyric acid (1 pyridin-2-yl-2-quinolin-4-yl-ethylidene)-hydrazide A mixture of 3-benzyl-4-bromo-butyric acid (2.0 g, 7.78 mmol) andthionyl chloride (6.0 mmol) is heated lo 80 "C for 2 h. The thionyl chloride is evaporated to yield 3-benzyI-4-bromo-butyryl chloride 2A g (99%), as a colorless liquid. 'H NMR (CDClj) 5 7.25-7.11 (m, 5H), 3.55-3.48 (m, 1H), 3.40-3.35 (m, 1H), 3.20-3.10 (m, 1H), 3.00-2.90 (m, IH), 2.80-2.70 (m, 2H), 2.60-2.57 (m, 1H). A solution of (l-pyridin-2-yl-2-quinolin-4-yl-ethylidene)-hydrazine{2.25 g, 8.40 mmol) in anhydrous dichlorometham; (100 mL) and pyridine (1.81 mL, 22.4 mmol) is cooled to -78 °C, treated with a solution of 3-benzyl-4-bromo-butyryl chloride (2.1 g, 7.8 mmol) in dichloromethane (10 mL), and stirred for 2 h. The mixture is treated with methanol (3 mL), stirred for 10 min, and diluted with saturated ammonium chloride solution (30 mL). The mixture is dik ted with dichloromethane (300 mL), washed with water (2 x 50 mL) and brine (50 mL), dried with anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue is precipitated from ether to yield the title compound, 2.3 g (60%), as a pale yellowish solid PREPARATION 130 7-Mt*hyl-4-methyl-quinoline A solution of 3-meihyl-phenylamine (1 eq), in 1,4-dioxane is stirred and cooled to S approximately 12 °C. Sulfuric acid (2 eq.) is slowly added and heated at reflux. Methylvinyl ketone (l.S eq) is added dropwise into the refluxing solution. The solution is heated for 1 h after addition is complete. The reaction solution is evaporated to dryness and dissolved in methylene chloride. The solution is adjusted to pH 8 with 1 M sodium carbonate and extracted with three times with water. The residue is chromatographed on SiC>2 (70/30 hexane/ethylacetate) to yield the title compound. MS ES+m/e= 158.2 (M+l). PREPARATION 148 ] -(2-Pyridyl)-2-(4-quinolyl)elhan-l -one In a 3-neck 3-liter round bottom flask equipped with two addition funnels is dissolved lepidine (10.0 mL, 75.63 inmol) in tetrahydrofuran (200 mL). One addition funnel is charged with ethyl picolinute (20.43 mL, 151.26 mmol) and the other with 0.5 M potassium bis(trimethylsilyl)amide (166.4 mL, 83.19 mmol) in toluene. The solution is cooled to -78 °C and the base added to the reaction mixture dropwise over 40 min. The reaction mixture is stirred an additional 1.5 h and ethyl picolinate is added rapidly. The ice bath is removed and the reaction mixture stirred at ambient temperature for 3 h. The reaction is quenched with water (20 mL) and after 5 min formic acid added until the pH is slightly less than 7. The mixture is concentrated in vacuo and partitioned between ethyl acetate (300 mL) and brine-sodium bicarbonate (300 mL) mixture. The organic layer is washed with brine and sodium bicarbonate, dried over sodium sulfate, and concentrated. The product is chromttographed on SiO2 (27-30 % acetone in hexane) to yield 15.31 g (82%) of a yellow-brown sol id. MSES+m/e249(M+l). PREPARATION 205 2-(4-Fluoro-phcnyl)-3-oxo-3-t6-lrinu«romethyl-pyridin-2-yl)-propionilrile A solution of4-fluorophenylitcetonitril«: (0.12 mL, 1.0 mmol) in dry tetrahydrofuran (2 mL) is treated dropwise with potassium bis(trimethylsilyl)amide (0.5 M toluene, 3.0 mL, 1.5 mmol) at 0° 0 under an atmosphere of nitrogen. The mixture is stirred 10 min then 6-trifluoromethyl-pyridine-2-carbothioic acid S-(4-chloro-phenyl) ester is added all at once. The mixture is allowed to warm to room temperature then warmed to reflux for 10 min, at which time the reaction is complete by TLC (methylcne chloride). The mixture is allowed to cool then poured into 10% citric acid and extracted into methylene chloride. The methylene chloride solution is dried over magnesium sulfate and concentrated in vacuo. T ie residue is purified on a silica gel cartridge prepared with hexane then eluted witlti methylene chloride to yield 204 mg (66 %) 2-(4- fluoro-phenyl)-3-oxo-3-(6-trifluoromethyl-pyridin-2-yl)-propionitrile. MS ES' m/z 307 (M-l). PREPARATION 206 2-(3-Chloro-4-fluoro-phenyl)-J-(6-methyl-pyridin-2-yl)-ethanone A dispersion of sodium hydride, (60% in mineral oil, 0.7 g, 17.7 mmol) is added to ethanol (25 mL). When gas evolution ceases, 3-chloro-4-fluorophenylacetonitrile (Fluorochemicals, 2.0 g, 11.8 mmol) and 6-methyl-pyridine-2-carboxylic acid methyl ester (1.8 g, 11.8 mmol), are added. The mixture is refluxed for 2.5 h and adjusted to pH 7 with 1 N hydrochloric acid. The mixture is concentrated in vacuo. Concentrated hydrochloric acid (50 mL) is added to the mixture after which it is refluxed for 1.5 h. The mixture is poured over ice and adjusted to pH 8 with 5 N sodium hydroxide. The mixture is extracted with rnethylene chloride and the organic portions dried over anhydrous sodium sulfate. The mixture is filtered and concentrated in vacuo to yield the title compound, 2.1 g (68%), as i, yellowish solid. 'H NMR (CDClj) 8 7.86-7.83 (m, 1H), 7.73-7.71 (m, 1H), 7.42-7.33 (m, 2H), 7.26-7.04 (m, 2H), 4.49 (s, 2H), 2.65 (s, 311). PREPARATION 231 l-(6-Methylpyridia-2-yl)-2-p-tolyl-ethanone To a slurry of magnesium turnings (406 mg, 16.7 mmol) in toluene (10 mL) is added 4-methylbenzylchloride (10 mg, 0.06 mmol) dropwise in tetrahydrofuran (0.2 mL). Two drops of 1,2-dibromoethane are added, the mixture heated to 50 °C, and allowed to cool to room temperature. This process is repeated until reaction initiates. 4- Methylbenzylchloride (1.5 g, 10 mmol) in tetrahydrofuran (7 mL) is added slowly while keeping the internal temperaturr below 32 °C. After the addition is complete the reaction is stirred at room temperature fcr I h. The reaction mixture is added dropwise over 5 minutes to a solution of 6-methyl-pyridine-2-carboxylic acid methoxy-methyl-amide (Prep 250,1 g, 5.6 mmol) in toluene (5 mL). The reaction is stirred for an additional 45 minutes. The reaction is quenclied with I N hydrochloric acid and stirred for 30 minutes. The aqueous layer is neutralized with saturated sodium bicarbonate and extracted twice with ethyl acetate. The combined organic extracts are washed with brine, dried (sodium sulfate), filtered and concentrate in vacuo. The crude residue is chromatographed on S1O2 (50% ethyl acetate/hexane to 75% ethyl acetate/hexane) to yield the title compound, 633 mg (25%), as a brown oil. MSES+m/e226(M+l) PREPARATION 213 2-(4-Fluoro-phenyl)-1^6-trifluoromethyl-pyridin-2-yl)-ethanoiic A slurry of 2-(4-fluoro-pl»enyl)-3-oxo-3-(6-trifluoromethyl-pyridin-2-yl)- propionitrile (1.4 g, 4.4 mmol) in 48% HBr is warmed to reflux for 8 h, allowed to stand at ambient temperature 16 h, then warmed at reflux for 8 h. The mixture is extracted with ether, treated with a small amount of sodium bicarbonate, extracted with ether, made basic with solid sodium hydroxide, and extracted again with ether. Ethereal extracts are combined, dried over magnesium sulfate, and concentrated in vacuo to a dark oil. The residual oil is purified on a silica gel cartridge prepared with hexane then eluted with methyl ene chloride to yield 816 ing (65%) of the title compound as a dark oil. MSESrn/z282(M-l). PREPARATION 229 |2-QuinuIin-4-yl-]-(3-fri(lluoromcilhyl-phenyl)-elhylidene]-hydrazine A solution of 2-quinolin-4->l-l-(3-trifluoromeihyI-phenyl)-ethanone (1.0 g, 3.2 mmol) in ethanol (13 mL) is cooled to 0 °C and treated with hydrazine (0.6 g, 19 mmol) and concentrated hydrochloric acid (0.13 mL, 1.6 mmol). The mixture is refluxed for 2 h and concentrated in vacuo. The residue is taken up in dichloromethane and washed with saturated sodium bica/bonate (30 mL), water (2 x 30 mL), and brine (30 mL). The solution is dried over anhydrous sodium suliate and filtered. The filtrate is concentrated to yield the title compound, 1.0 g (97%), as a pale yellow foam. 'H NMR (CDC13) 6 8.80 (m, 1H), 8.28-8.05 (m, 3H), 7.90-7.40 (m, 4H), 7.20-7.05 (m, 2H), 5.50 (s, 2H), 4.45 (m, 2H). PREPARATION 2S2 4-BcnzyJ-)-(]-pyridin-2-yl-2-quinolin-'l-yJ-ethylidcncamino)-pyrroHdin-2-one A mixture of 3-benzyl-4-bromo-butyric acid (l-pyridin-2-yl-2-quinolin-4-yl- cthylidene)-hydrazide (PREP. 70, 0.8 g, 1.6 mmol) in leirahydrofuran (26 mL) at 0 °C is treated with NaH (60% in mineral oil, 0.086 g, 2.2 mmol). The mixture is wanned to room temperature and stirred for 2 h. Saturated ammonium chloride (2 mL) is added and volatiles removed in vacuo. The residue is chromatographed on SiC>2 (90% ethyl acetate/hexanes followed bydichlotomethane:methanol:ammonium hydroxide/94:5:1) to yield the title compound, 0.4 g (45%), as & yellowish foam. 'H NMR (CDCh) 6 8.86-8.82 (m, 1.H), 8.70-8.60 (m, 1H), 8.30-8.05 (m, 3H), 7.80-7.30 (m, 4H), 7.30-7.20 (m, 5H), 6.85-6.H0 (m, 1H), 5.20-4.85 (m, 2H), 3.05-2.95 (m, 2H), 2.30-2.15 (m, 3H), 2.00-1.90 (m, 2h). PREPARATION 286 4-(3-Mcihoxy-phcnyl)-l-(] pyridin-2-yl-2-quinolin-4-yl-ethylideneainino)- pyrroUdin-2-one A solution ofl-pyridin-2-yl-2-quinolin-4-yl-ethanone, (0.25 g, 1 mmol) and pyridine (0.242 mL, 3 mmol) in acetic acid (2 mL) is added to 1-amino-4-(3-methoxy- phenyl)-pynrolidin-2-one, (0.2 g, I mmol) at room temperature under nitrogen. The mixture is stirred 18 h and concentrated in vacuo. The residue is chromatographed on SiOj (2% methanoi/dichloromethane) to yield the title compound, 0.25 g (57%), as a yellow foam. 'H NMR (CDC13): S 8.75 (d, J - 4.5 Hz, 1H), 8.65 (d, J = 4.5 Hz, 1H), 7.70-8.20 (m, 3H), 7.20-7.60 (m, 3H), 6.70-6.85 (m 3H), 6.40-6.55 (m, 3H), 5.25 (d, J = 16.7 Hz, 1H), 4.70 (d, J = 16.7 Hz, 1H), 3.70 (s, 3H>, 3.45-3.60 (m, 1H), 3.10 (dd, J = 8,9.3 Hz, 1H), 2.25- 2.80 (m,3H). PREPARATION 358 t (y?)-5-Bcn2yloxymethy)-l-|2-(4-fluoro-phcnyl)-l-(6-mcthyl-pyridin-2-yl)- eth)tideneamino]-pyrrnlidin-2-one Boron trifluoride etherate (0.25 mL, 1 -98 mmol) is added to a solution of 2-(4- fluoro-phenyl)-l-(6-methyl-pyridin-2-yl)-ethanone (0.45 g, 1.98 mmol) in tetrahydrofuran (6.6 mL) under nitrogen and stirred for 30 min. A solution of (•/?)-!- amino-5-benzyloxymethy]-pyrrolidin-2-one (0.43 g, 1.98 mmol) in tetrahydrofuran (1.0 mL) is added and the resulting mixture is stirred for 1 h. The mixture is concentrated in vacuo and the residue chromatographed on a SiC>2 column (30% ethyl acetate/hexanes) to yield the title compound, 380 nig (45%)., as a yellow foam. 'H NMR (CDCI3): 5 7.81 (d, J = 7.8 Hz, ]H), 7.55 (t, J = 7.8 Hz, 1H), 7.11-7.32 (m, 8H), 6.81 (td, J = 8.7, 2.0 Hz, 2H), 4.45 (s, 2H), 4.30-4.43 (m, 2H), 3.80 (m, 1H), 3.39-3.51 (m, 2H), 2.51-2.63 (m, 4H), 2.23-2.41 (m, 1H), 1.86-2.04 (m, 2H). PREPARATION 359 4-(4-Chloro-phenyl)-l-|2-(4-fluoro-phenyl)-l-(6-methyl- pyridin-2-)l)-cthylideneaminoj-pyrrolidin-2-one A method similar to PREPARATION 358, except employing 1-amino-4-(4- chloro-phenyl)-pyrrolidin-2-one (1.47 g, 7.0 mmol), is used to yield the title compound, 1.56 g (53%), as a yellow foam. 'H NMR (CDCI3): 5 7.55-7.66 (m, IH), 7.15-7.45 (m, 7H), 6.89-7.07 (m, 3H), 4.61 (d, J - 15.4 Hz, IH), 4.28 (d, J = 15.4 Hz, IH), 3.54-3.71 (m, 2H), 3.26-3.42 (m, IH), 2.75- 2.89 (m, IH), 2.58 (s, 3H), 2.46-2.56 (m, IH). PREPARATION 368 2-(6-Melhyl-pyridin-2-yl)-5,6-dthydro-4H-pyrrolo| 1,2-b]pyrazole-3-carboxylic acid ethyl ester A solution of (6-methyl-pyridin-2-yI}-propynoic acid ethyl ester (3 g, 15.9 mmol) and 3a H-pyrrolidino[l,2-C] 1,2,3-oxadiazolin-3-one (2 g, 15.9 mmol) is heated in xylcne (50 mL) at 150 °C for 48 h. The mixture is cooled and concentrated in vacuo. The crude residue is chromatographed on SiO»(ethyl acetate) to give the title compound, 1.6 g (37%), as a brown solid. MSES+m/e272(M+l). PREPARATION 369 2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo|l,2-b]pyrazolc-3-carboxylicacJd A solution of 2-(6-methyl-p)'ridin-2-yl)-5,6-dihydro-4H-pyrrolo[l ,2-b]pyrazole-3- carboxylic acid ethyl ester (1.6 g, 5. > mmol) and 2 N sodium hydroxide (6 mL, 29 mmol) in absolute ethanol (50 mL) is reflu> cd for 5 h. The mixture is cooled to room temperature and concentrated in vacuo. The residue is suspended in water and acidified to pH 5 with 1 N hydrochloric acid. The aqueous solution is extracted three times with dichloromethane. The organic extracts are combined, dried (sodium sulfate), filtered, and concentrated in vacuo to yield the title compound, 1.4 g (97%), as a white solid. MSESm/e242(M-l). PREPARATION 370 3-Br«mo-2-(6-mclhyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo|l,2-bJpyrazole A solution of 2-(6-methyJ-pyiidin-2-yl)-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazole-3- carboxylic acid (1.4 g, 5.8 mmol) in iV.A^dimethylformamide (20 mL) is treated with N- bromosuccinamide (1 g, 5.6 mmol) and stirred at room temperature for 16 h. The mixture is diluted with ethyl acetate and washed three times with water, once with brine, dried (sodium sulfate), filtered, and concentrated in vacuo to yield the title compound, 1.5 g (94%), as light yellow solid. MSES+m/e278(M+l). PREPARATION 371 4-(2-Pyridin-2-yl-5,6-dihydro-4H pyrrolofl,2-b)pyrazol-3-yl)-quinoline-7-carboxylic acid Lithium hydroxide monohydratc (0.65 g, 15.6 mmol) is added to a solution of 4- (2-pyridin-2-yl-5,6-dihydro-4H-pynolo[ 1,2-b]pyrazol-3-yl)-quinoline-7-carboxylic acid methyl ester (1.44 g, 3.89 mmol) in 2:1 tetrahydrofuran/water (30 mL), stirred at room t temperature for 18 h, and concentrated in vacuo. The residue is purified by SCX resin, (2 N ammonia in methanol), to yield the title compound, 1.22 g (88%), as a tan solid. 'H NMR (DMSO-rf6): 8 8.91 (m, 1H), 8.55 (rn, 1H), 7.48-7.85 (m, 7H), 7.41 (m, 1H), 7.09 (m, 1H), 4.22 (m, 2H), 2.81 (m 2H), 2.60 (m, 2H). PREPARATION 374 (5>6-Ben2yloxymelhyl-3-(4-nu«»ro-phcnyl)-2-(6-mclhyl-pyridin-2-yl)-5,6-dihydro- 4Hpyrrolo|]l,2-b]pyn»zole A method similar to PREPARATION 360, except employing (5)-5- benzyloxymethyJ-]-[2-(4-fluoro-pJienyl>]-(6-methyl-pyTidin-2-yl>ethylideneamino3- pyrrolidin-2-one (0.5 g, 1. J 6 mmol), is used lo yield the title compound, 325 mg (68%), as pale brown oil. 'H NMR (CDCh): 6 7.50 (t, J « 8.8 Hz, 1H), 7.17-7.47 (m, 8H), 6.96-7.06 (m, 3H), 4.61 (m, 1H), 4.50 (s, 2H), 3.98 (dd, J = 9.8, 3.2 Hz, 1H), 3.87 (dd, J = 9.8,5.6 Hz, 1H), 2.68- 3.05 (m, 4H), 2.54 (s, 3H). MSAPCI+m/c414(M+l). PKEPARATION 375 5-Chloromethyl-2,2-difluoro-benzo|l,3]dioxolc A solution of (2,2-difhioro-benzo[l,3]dioxol-5-yl)-methanol (1.0 g, 5.32 mmol) in carbon tetrachloride (10.6 mL) is added to polymer-supported triphenylphospine (3.5 g, 3 mmol/g, 10.6 mmol) at room temperature. The reaction is heated for 3 h at 80 °C, cooled to room temperature, filtered, and the solids washed with dichloromethane. The filtrate is concentrated in vacuo to yield the title compound, 0.79 g (72%), as a clear, orange oil. MSCI+m/e207(M+l). PREPARATION 378 Methanesulfonic acid 2-pyridii»-2-yl-3-quinolin-4-yl-5,6-dihydro-4H-pyrrolo|l,2- b]pyrazol-6-ylmcthyl ester A solution of [2-(6-methyl-pyridin-2-yl)-3-quinolin-4-yl-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-6-yl]-methanol (30mg, 0.07 mmol) and 4-dimethylaminopyidine (catalytic) in pyridine (0.2 mL) is cooled to 0 °C and treated with methanesulfonyl chloride (8 mL, 0.105 mmol) and stirred for 30 min. The mixture is stirred at room temperature for 30 min, diluted with ethyl acetate (20 mL), washed with water and brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to yield the title compound, 30 mg (86%,) as a yellow oil. 'H NMR (CDC13): 5 8.90 (d, J = 4.0 Hz, IH), 8.45 (d, J = 4.0 Hz, 1H), 8.15 (d, J = 8.5 Hz, 1H), 7.55-7.70 (m, 2H), 7.36-'.48 (m, 2H), 7.05-7.30 (m, 3H), 4.80-4.90 (m, 2H), 4.65-4.75 (m, 1H), 2.65-3.05 (m, 7H). PREPARATION 387 4-j4-(2-Pyridin-:!-yl-S,6-dihydro-4H-pyrrolo|l,2-bJ py razol-3-yl)- q u inolin-7-y loxy]-piperidine-l - carboy lie acid lert-buty) ester To a suspension of 4-(2-pyridm-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b)pyra2oI-3-yl)- quinolin-7-ol (0.27 g, 0.84 mmol) irii WN-dimethylformamide (15 mL) is added 4-bromo- piperidine-1-carboxylic acid tert-buiyl esier (0.29 mL, 2.28 mmol) and cesium carbonate (1.5 g, 4.57 mmol. The mixture is heated at 80 °C for 48 h and concentrated in vacuo. The residue is taken up in dichlororr ethane, washed with water and brine, dried over sodium sulfate, and concentrated in vacuo. Purification by flash chromatography (S1O2, 7% methanol in dichloromethane) yields the title compound, 262 mg (61 %,) as a yellow oil. MSES+m/e512(M+l). Regioisomer ]: 'H NMR (CDC13) 5: 8.26 (d, 2h), 8.04 (s, 1H), 7.69 (d, 1H), 7.63 (t, 1H), 7.39 (t, 1H), 7.35 (t, 1H), 7.25 (d, 1H), 6.79 (t, 1H), 4.47 (quartet, 2H), 4.31 (t, 2H), 2.82 (m, 2H), 2.65 (quintet, 2H), J .40 (t, 3H); MS ES* m/c 385 (M+l). Regioisomer 2: 'H NMR (CDCIj) 8: 8.39 (d, JH), 3.27 (d, 1H), 8.20 (s, 1H), 7.90 (d, 1H), 7.65 (t, 1H), 7.37 (t, 1H), 7.18 (t, \U), 6.57 (d, 1H), 4.26 (t. 2H), 3.26 (t, 2H), 2.70 (quintet, 2H), 1.38 (t, 3H); MS ES+ m/e 385 (M+l). PREPARATION 395 2-(2-Hydroxyelhyl)-3-hydro>ymelhyl-.'>-pyridin-2-yl-4-quinolin-4-yl-pyrazole To a solution of 2-pyridin-2-yl-3-quiinolin-4-yl-pyrazolo[5,l-c]morpholin-4-one (0.50 g, 1.46 mmol) in tetrahydrofuran (20 mL) is added L1AIH4 (0.50 g, 13.1 rnrnol) at room temperature. The mixture is stirred for 2 h quenched with 1 N sodium hydroxide solution, and partitioned between dichloromethane and water. The organic portion is dried (sodium sulfate), filtered, anc concentrated in vacuo. The residue is chromatographed on SiO2 (10% mcthanol/dichloromethane) to yield the title compound, 0.35 g (70%), as an off-white solid TOF MS ES+ exact mass calculated for C20H19N4O2 (p+1): m/z = 347.1508. Found: 347.1496. PREPARATION 397 3-Elhoxycarbonfl-5-pyridiii-2-yl-4-quinolin-4-yl-pyra2ole A solution of 2-quinolin-4-yl-l-pyiridin-2-yl elhanone (1.00 g, 4.0 mmol) and hydrazine monohydrate (1.0 ml.) in ethanol (200 mL) is heated at reflux for 2 h. The mixture is concentrated in vacua to dryness, the residue dissolved in pyridine (SO mL), cooled to 0 °C, and treated with ethyl oxalyl chloride (0.60 mL, 5.4 mmol) dropwise over 20 min. The mixture is warmed to room temperature, stirred for 2 h, and heated at reflux for 3 h. The mixture is concentrated in vacuo and the residue partitioned between dichloromethane and water. The organic portion is dried (sodium sulfate), filtered, and concentrated in vacuo to yield tine title compound, 0.6 g (44%,) as a white solid which is crystallized from ether. 'H NMR (CDC13): 6 12.43 (br s, 1H), 9.02 (d, J = 5 Hz, 1H), 8.56 (br s, 1H), 8.32 (d, J = 7 Hz, 1H), 7.76 (t, J = 7 Hz, 1H), 7.65 (d, J = 8 Hz, 1H), 7.46 (m, 2H), 7.33 (br s, 1H), 7.17 (t, J = 7 Hz, 1H), 4.11 (m, 1H), 0.90 (t, J = 7 Hz, 1H). MS ES+m/e 345.0 (M+l). PREPARATION 398 5-Pyridin-2-yl-4-quinolin-4-yl-2H-pyrazol-3-ol To a solution of (l-pyridin-2-yl-2-quinolin-4-yl-ethylidene)-hydrazine (2.0 g, 7.6 mmol) in pyridine (20 mL) at 0 °C is added ethyl chloroformate (2 mL) dropwise. The mixture is warmed to room temperature and stirred for 2 h. The solution is refluxed for 12 h and concentrated in vacuo The residue is treated with dichloromethane/methanol and the precipitate collected by vacuum filtration. The precipitate is triturated with ethanol to yield the title compound, 300 mg (13%), as a white solid. MS ES+m/e 288.9 (M+l). PREPARATION 401 4-|4-(2-Pyridiii-:!-yl-5,6-dihydro-4H-pyrrolo|l,2-b| pyrazol-3-yl>quinolin-7-yloxy)-piperidine-]- carbo) ylic acid ilcrt-butyl ester To a suspension of 4-(2-pyridin-2-yl-5,6-dihydro-4H-pym>lo[l,2-b]pyrazoI-3-yl)- quinolin-7-ol ( 0.27 g, 0.84 mmol) in 7V,JV-dimethylformamide (15 mL) is added 4-bromo- piperidine-1-carboxylic acid tert-bulyl ester (G.29 mL, 2.28 mmol) and cesium carbonate (1.5 g, 4.57 mmol). The mixture is heated at 80 °C for 48 h and concentrated in vacuo. The residue is taken up in dichloromethane, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated in vacuo. The residue is chromatographed on SiO2 (7% methanol in dichloromethane) to yield the title compound, 262 mg (61%), as a yellow oil. MSES+m/e512(M+l). PREPARATION 403 |4-(2-Pyridin-2-yl-5,6-dihydr(»-4H-pyrrolo|l,2-b]pyrazol-3-yl)-quinolin-7-yloxyJ- acctic acid To a solution of [4-(2-pyridiri-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazoI-3-yl)- quinolin-7-yloxy]-acetic acid ethyl ester (250 ring, 0.6 mmol) in methanol (4 mL) at room temperature is added 1 N lithium hydroxide (1.2 mL, 1.2 mmol). The mixture is heated at 60 °C for 4 h. The mixture is cooled to room temperature and concentrated in vacuo. The residue is taken up in water and acidified to pH = 6 with 1 N hydrochloric acid. The aqueous solution is extracted with dichloromethane 5 times. The combined organic PWF.PARAIIUIN iyy |2.Methyl-2-({4-|2-(6-nielhyl-pyridin-2-yt)-5,6-dihydro-4H-pyrroIofM-bJpyra2oJ-3. yl]-quinoline-7carbonyl}-»roino)-propylj-carbamic acid ten-butyl ester To a solution of 4.[2-(6-mcthyl-pyriclin-2-y1)-5,6'dihydro-4H-pyiTolon,2- b]pyrazol-3-yl]~quinoline-7-carboxylic acid (0.16 g, 0.43 mmol), (2-amino-2-methyl- propyJ)-carbamic acid / hydroxybenzotriazole (0.06 g, 0.47 mmol)in .iichloromethane (8.6 mL)is added N.N- diisopropylethylamine (0.25 mL, 1.29 mmol) The mixture is stirred at room temperature for 18 hand concentrated in vacuo. The residue is taken up in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate and concentrated in vacuo. The residue is chromatographed on !>iO2 (methanol/dichloromethane / 2:98) to yield the title compound 0.21 g (91%) as a wh te solid. 'H NMR (CDCI.0 6 8.93-8.86 (m, 1H), 8.51 (s 1H), 7.79 (s, 2H), 7.39-7.23 (m, 2H), 7.08-7.00 (m, 1H), 6.93-6.85 (m, 1HX 5.32-5.20 (m, 1H), 4.42-4.31 (m, 2H), 3.41-3.32 (m, 2H), 2.89-2.78 (m, 2H), 2.75-2.61 (m, 2H), 2.26 (s, 3H), 1.54-1.41 (m, 15H). extracts are dried (sodium sulfate), filtered, and concentrated in vacuo to yield the title compound, 150 mg (65%), as an off white solid. MSESm/e385(M-l). PREPARATION 404 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo|J,2-b]pyrazol-3-yl)-7-(tetrahydro-furan-2- ylmethoxy)-quino)ine A mixture of methanesulftmic acid tetrahydro-furan-2-ylmethyl ester (0.70 g, 3.66 mmol), 4-(2-pyridin-2-yl-5,6-dih>dro-4H-pyuolo[l,2-b]pyrazol-3-yl)-quinolin-7-ol (400 mg, 1.22 mmol), and cesium carbonate (2.38 g, 7.32 mmol) in WAf-dimethylformamide (2.5 mL) is heated at 60 °C for 42 h. The mixture is concentrated in vacuo and the residue chromatographed to yield the title compound, 79 mg (15%), as a tan solid. MSAPC+m/e413(M+I). To a suspension of hexane-washed sodium hydride (60 % dispersion in mineral oil, 347 mg, 50 mmol) in 7V,W-diineiby)formaniide (20 mL) is added l-[2-(6-bromo- quinolin-4-yl)-l -pyridin-2-yl-ethylkfeneamino)-pyrrolidin-2-one (2.2 g, 5.37 mmol). The resulting mixture is heated at 80-85 "C under nitrogen atmosphere for 18 h. The reaction is adjusted to pH 2 and neutralized with solid sodium carbonate. The product is extracted with ethyl acetate, dried over sodium sulfate, and concentrated in vacuo. The residue is chromatographed on SiO2 (dichloronethane to 2% methanol/dichloromethane) to yield a colorless solid, 1.145 g (54 %). MS ES+m/e 391.2 & 393.2 (M+I). A mixture of 3-bromo-2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l ,2- b]pyrazolc (99 mg, 0.36 mmol), 3,4-methylcnedioxyphenylboronic acid (65 mg, 0.39 mmol), (PPhj^Pd (20 mg, 0.02 mmol), I N aqueous sodium carbonate solution (500 ^iL, 0.5 mmol) in toluene (5 mL) and methanol (1 mL) is purged with argon for 10 min and heated at 80 °C under nitrogen for 30 h. The mixture is cooled and partitioned between water and ethyl acetate, and the organic portion washed with water and brine, dried (sodium sulfate), filtered, and concentrated in vacuo. The crude residue is chromatographed on SiO2 (ethyl ncetate) to yield the title compound, 10 mg (9%), as a yellow solid. MSES+m/e320(M+l). To a mixture of sodium acetate (0.84 g, 10.2 mmol) and [1,1 '- bis(diphenylphosphino)ferrocene]dichloropalladium (11):CH2C]2 (42 mg, 0.05 mmol) in methanol (40 mL) is added 6-bromo-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrololl,2- b]pyrazol-3-yl)-quinoline (1.0 g, 2.56 mmol). The mixture is heated at 90 °C under 68 psi carbon monoxide for 24 h. The mixture is cooled, filtered, and concentrated in vacuo. The product is partitioned between ethyl acetate and water. The organic layer is dried over sodium sulfate and concentrated n vacuo. The residue is chromatographed on SiO2 (dichloromethane to 2% methanol/dichloromethane) to yield a solid, 918 mg (97%). MS ES+m/e 371.2 (M+l). To a solution of 2-(2-hydroxyeihyl)-3-hydroxyrnethyl-5-pyridin-2-yM- 4-yl-pyrazole, (0.10 g, 0.29 mmol) in tetrahydrofuran (10 mL) cooled at 0 °C is added NaH (0.04 g, 50% in mineral oil). The mixture is stirred for 2 h at room temperature and methanesulfonyl chloride (0.065 g, 0.57 mmol) is added dropwise over 30 min. The reaction is quenched with water and extracted into ethyl acetate. The organic layer is washed with water,.dried (sodium sulfate), filtered, and concentrated in vacuo. The residue is chromatographed on S1O2 [10% methanol/dichloromethane) to yield the title compound, 31 mg (33%), as a white solid. TOF MS ES+ exact mass calculated ior C20H,6N4O (p+1): m/z = 329.1402. Found: 329.1409. A mixture of3-ethoxycarbonyi-5-pyndin-2-yl-4-quiriolin-4-yi-pyra2OJe (\).55 g, 1.00 mmol), 2-bromoethanol (0.15 g, 1.12 mmoll), and cesium carbonate (0.50 g, 1.5 mmol) in W.yV-dimethylformamide (20 mL) is heated at 60 °C for 2 h. The mixture is cooled to room temperature and poured into ethyl acetate (60 mL). The organic portion is washed with water, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue is chromatographed on SiO2 (ithyl acetafe/hexane) to yield the title compound, 110 nig (32%). A solution of 7-(3-chloio-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl)-quiiioline (54 mg, 0.13 mmol), sodium iodide (5 mg, 0.03 mmol), and 2 N dimethylamine in tetrahydrofuran (3 mL, 6 mmol) in N.N- dimethylformamide (5 mL) is heated at 100 °C for 48 h. The mixture is cooled and concentrated in vacuo. The residue is chromatographed on S1O2 (100% ethyl acetate to 10% methanol in ethyl acetate) to yield the title compound, 41 mg (74%), as a brown solid. TOF MS ES+ exact mass calculated for C25H28N5O (p+1): m/z = 414.2294 Found: 414.2313 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinohn-7-ol (0.100 g, 0.305 mmol), N-(3-bromoprof.yl)-phthalimide (0.163 g, 0.609 mmol, 2.0 equiv) and cesium carbonate (0.248 g, 0.761 mmol, 2.50 equiv) are combined in N.N- dimethylformamidc (1.0 mL) and the reaction is heated at 60 °C for 48 hours. The reaction is diluted with water (1 mL) ami the reaction mixture is partitioned between ethyl acetate (6 mL) and water (5 mL). The organic layer is removed and placed on alO g SCX resin column. The resin is washed sequentially with dichloromethane (20 mL) and 4:1 dichloromethane/2 N ammonia in melhacK)! (125 mL). The latter fractions are evaporated to dryness and the residue is subjected to chromatography on silica gel (20 g) (9:1 ethyl A solution of (R)-(-)-5- mmol) and heated at 60 °C for 5 h. The reaction mixture is diluted with N,N- dimethylformamide (1 mL) and4H;2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[l,2-b]pyra2ol- 3-yl)-quinolin-7-ol (200 mg, 0.91 mmol) added. The mixture is stirred at 60 °C for additional 16 h, cooled to room temperature, and partitioned between ethyl acetate and water. The organic portion is washed three times with water, once with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The crude residue is chromatographed on SiO2 (89% dichloromethane 10% methanol 1 % concentrated ammonium hydroxide) to yield the title compound, 32 mg (8%), as a light red solid. MSES+m/e426(M+l). To a solution of 4-[2-(6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-yl]-quinoline (133 ing, 0.41 mmol) in dichloromethane is added m- chloroperoxybenzoic acid (248 mg, 1.44 mmol) and the resulting mixture stirred for 3 h. The mixture is diluted with dicMoromethane and washed twice with saturated aqueous sodium bicarbonate solution, once with brine, dried (sodium sulfate), filtered and concentrated in vacuo to yield the title compound, 140 mg (96%), as white foam. TOF MS ES+ exact mass calculated for C2,H,9N4O2 (p+1): m/z = 359.1508. Found: 359.1516. Nitrogen is bubbled through a solution of 7-bromo-4-[2-(6-methyl-pyridin-2-yl)- 5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl|-quinoline (0.050 g, 0.12 mmol), tributylamine (0.032 mL, 0.17 mraiol), methyl acrylaie (0.027 mL, 0.24 mmol), and N.N- dimethylformamide (0.5 mL) in toluene (1.0 mL) for 20 min. Pd(OAc)2 (0.002 g, 0.006 mmol) and tri(o-toly])phosphine (0.007 g, 0.021 mmol) are added and nitrogen bubbled through the reaction mixture for 0 min. The mixture is heated to 80 °C for 24 h. An additional portion of Pd(OAc)2 (0.002 g, 0.006 mmol) and tri(o-tolyl)phosphine (0.007 g, 0.021 mmol) is added and heating continues for another 24 h. The reaction is cooled and concentrated in vacuo and the residue chromatographed on SiO2 (2% methanol in methylene choloride) to yield the title compound, 0.49 g (97%), as a yellowish solid. MS APC1+ m/e 411 (M+l). Nitrogen is bubbled through a solution of 7-bromo-4-[2-(6-methyl-pyridin-2-yl)- 5,6-dihydro-4H-pyrrolo[1,2-b]pyra2.ol-3-yl]-quinoline (0.050 g, 0.14 mmol) and tributylvinyltin (0.079 mL, 0.22 mmol) in toluene (2.0 mL) for 20 min. Pd(PPh3)2Cl2 is added and nitrogen bubbled througli the reaction mixture for another 10 min. The mixture is heated to 90 °C for 24 h, concentrated in vacuo, and the residue chromatographed on SiC>2 (elute with 2% methanol in methylene choloride) to yield the title compound, 0.030 g (61%), as a yellowish solid. MSAPa+m/e353(M+l). Zinc(II) chloride (0.34 mL, 1.0 M solution, 0.34 mmol) is added, at room temperature with stirring, to a solution of benzyl magnesium chloride (0.15 mL, 2.0 M solution, 0.31 mmol) in tetrahydrofuran (1 ml.). After 15 min, Pd(PPh3)2Cl2 (5.4 mg, 0.0076 mmol) is added followed by a solution of 4-[2-(6-bromo-pyridin-2-yl)-5,6- dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl]-quinoline (60 mg 0.153 mmol) in tetrahydrofuran (1 mL). The reaction mixture is stirred for 18 h at room temperature and quenched with saturated aqueous ammonium chloride (1 mL). The reaction mixture is concentrated in vacuo, filtered, and the residue chromatographed on SiC>2 (20-50% acetone/hexanes) to yield the title compound, 33.4 mg (54%), as a white solid. MS (CI, methane) m/e 403 (M+l). To a solution of 4-[2-(6-methyl-pyridin-2-yl>5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-yl]-quinoline-7-carboxy*ic acid ethyl ester (250 mg, 0.6 mmol) in methanol (4 mL) at room temperature is added 1 N lithium hydroxide (1.2 mL, 1.2 mmol). The mixture is heated at 60 °C for 4 h. The mixture is cooled to room temperature and concentrated in vacuo. The mixture is diluted with water and acidified to pH 6 with 1 N hydrochloric acid. The aqueous solution is extracted with dichloromethane 5 times. The combined organic extracts are dried sodium sulfate), filtered, and concentrated in vacuo to yield the title compound, 150 mg (65%), as an off white solid. MSESm/e369(M-l). A mixture of l-(3-dimetltylaminopropyI)-3-ethylcarbodiimide hydrochloride, (53 mg, 0.30 mmol), HOBT, (24 mg, 0.28 mmol), cyclopentylamine (0.03 mL, 0.30 mmol), and 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline-7-carboxylic acid (90 mg, 0.25 mmol) in dichloromethane (1 mL) is stirred room temperature for 18 h. The mixture is concentrated in vacuo and the residue chromatographed on S1O2 to yield the title compound, 31 mg (31 %,) as a white solid. MSAPC+m/e424(M+l). To a solution of [4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-acetic acid (150 mg, 0.39 mmol) in dichloromethane (3 mL) is added oxalyl chloride (490 mg, 3.9 mmol) and 1 drop of N.JV-dimethylformamide. The mixture is stirred at room temperature for 5 h, concentrated in vacuo, and residual solvents removed by co-evaporation three times with chloroform to yield [4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[l,2-b]pyrazos-3-yl)-quinolin-7-yloxy]-acetyl chloride as a yellow solid. To a solution of [4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo(l,2-b]pyrazol-3-yl>- quinolin-7-yloxy]-acetyl chloride (50 mg, 0.12 mmol) in dichloromethane at room temperature is added 1-methyl-piperazine (62 mg, 62 mmol) and the mixture stirred for 2.5 h. The mixture is partitioned between dichloromethane and water, the organic portion dried (sodium sulfate), filtered, and concentrated in vacuo. The crude residue is chromatographed on SiO2 (89% dichloromethane 10% methanol 1% concentrated ammonium hydroxide) to yield the title compound, 28 mg (48%), as a light brown solid. MSES+m/e469(M+l). A solution of 4-[2-(6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yl]-quinoline-6-carboxylic acid methyl ester (0.055 g, 0.14 mmol) in 2-N.N- dimethylaminoelhylamine (1.5 iwL) is healed at 100 °C for 24 h. The mixture is concentrated in vacuo and the residue chrornatographed on SiO^ (100% ethyl acetate) to yield the title compound, 0.045 g (74%), as a yellowish solid. MS APCI+ m/e 441 (M+l). Molecular chlorine is bubbled through a solution of 7-benzylsulfanyI-4-(2- P)Tidin-2-yl-5,6H^ihydro-4H-pyl^olo[I,2-b]pyrazoJO-yl)-quino^ine (190.2 mg, 0.44 mmol) in water (0.3 mL) and glacial acetic acid (1.8 mL) for 10 min. The resultant solution is divided into six 4 mL vials and each is concentrated. One vial is treated with 7 M ammonia in methanol for 10 min. The mixture is concentrated in vacuo and the residue chromatographed on SiO? (dichloromethane, 2%, and 5% methanol/dichloromethane) to yield the desired product, (17 mg), as colorless oil. MS ES*m/e 392.3 (M+l). A solution of 7-bromo-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3- yl)-quinoline (135.0 mg, 0.34 mmoi), sodium /er/-butoxide (64.0 mg, 0.62 mmol), and benzophonone imine (91.0 mg, 0.51 mmol) in toluene (3 mL) is degassed with nitrogen for 20 min. To this solution is added tri(dibenzyldeneacetone)-dipa11adium(0) (1.0 mg, 0.0011 mmol) and 2,2'-bis(dipheny«phosphine)-l,l'-binaphthyl (J.5 mg, 0.0024 mmol) and the mixture degassed with nitrogen for another 10 min. The mixture is heated at 80 °C for 24 h, cooled to room temperature, quenched with saturated ammonium chloride, and extracted with chloroform. The combined organic portions are washed with water and brine, dried (sodium sulfate), and concentrated in vacuo. The residue is dissolved in 1 M hydrochloric acid (5 mL )and heated at reflux for 2.5 h. The mixture is concentrated in vacuo and the residue neutralized with saturated sodium bicarbonate. The resultant mixture is extract with chloroform and the organic extracts concentrated in vacuo to yield the desired product as a yellow solid, 96.5 mg (85%). MS ES+m/e 327.9 (M+l). A mixture of dimethylamimo-acetyl chloride (620.0 mg, 13.33 mmol), 4-(2- pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolin-7-ylamine (75 mg, 0.23 mmol), and 4-N, TV-dimethylaminopyridine (10.2 mg, 0.09 mmol) in drypyridine (1 mL) is refluxed for 72 h. The mixture is treated with saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer is washed with brine, dried (sodium sulfate), concentrated in vacuo, and the residue chromatographed on S1O2 ((5% to 20% methanol in dichloromethane) to yield a yellow oil, 62.3 mg (67%). MS ES'm/e 413.1 (M+l). To a mixture of 4-(2-pyridin-2-yl-5,6-dihydro-4H pyrrolo[ 1,2-b]pyrazol-3-yl> quinolin-7-ylamine (38.1 mg, 0.11 mmol) and 4-N, JV-dimethylaminopyridine (4.2 mg, 0.034 mmol) in dry pyridine (1 mL) is added 20% phosgene in toluene (80 nL, 0.76 mmol). The resulting mixture is stirred at 50 °C for 18 h, treated with N, N- dimethylethylendiame (0.5 mL), and stirred for 4 h. The mixture is concentrated in vacuo and the residue partitioned between eihyl acetate and brine. The organic layer is dried A 2 M solution of isopropyi magnesium chloride in tetrahydrofuran (65 uX, 0.13 mmol) is added lo solution of 7-biomo-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrroIo[l,2- b]pyrazol-3-yl)-quinoline (50.0 mg, 0.13 mmol) in tetrahydrofuran (1 mL) at room temperature with stirring for 2 h. The mixture is cooled to -78 °C and triethylamine (21.4 U.L, 0.154 mmol) and methanesuHonyl chloride (11 nL, 0.14 mmol) added. The mixture is warmed to room temperature and allowed to stand 18 h. The mixture is treated with water, extracted with ethyl acetatt:, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue is chromatog>raphed on S1O2 (dichloromethane to 75% ethyl acetate/dichloromethane) to yield the title compound as a solid, 4.5 mg (9%). MS ES+m/e 433.1 & 435.1 (M+1)- A solution of 4-[2-(6-rnethyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l ,2- b]pyrazol-3-yl]-quinoline-6-carboxylic acid methyl ester (0.06 g, 0.16 mmol) in tetrahydrofuran (1 mL) is cooled to -78 °C and degassed with nitrogen for 20 min. To this solution is added 3 M methylmagnesium chloride in tetrahydrofuran (0.17 mmol, 0.06 mL) and the resulting mixture stirred at 0 °C for 2 h. The mixture is treated with aqueous saturated ammonium chloride and extracted with ethyl acetate. The combined organic extracts are washed with brine, dried (anhydrous sodium sulfate), filtered, and concentrated, in vacuo. The residue is chromatographed on S1O2 (100% ethyl acetate) to yield the title compound, 17 mg (28%), as an off-white foam. MSAPCi+in/e385(M+l). To a solution of Preparation #21, 3-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl)-quinolin-7-ylsulfanyl)-propan-l-ol (25.0 mg, 0.062 mmol) in dry pyridine (0.1 mL) is added toluene sulfonyl chloride (60.0 mg, 0.31 mmol) and the resulting mixture stirred at room temperature for 72 h. Saturated sodium bicarbonate solution is added and the resulting solution extracted with ethyl acetate. The organic layer is washed with brine, dried (sodium sulfate), filtered, and concentrated in vacuo. Purification of the residue on S1O2 (5% to 10% methanol in dichloromethane) gives the desired product, 11.2 mg (43%). MS ES+m/e 421.1 (M+l). A solution of 1 M sulfuryl chloride in dichloromethane (20 mL, 20 mmol) is added to a solution of 7-bromo-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolop^b]pyrazol- 3-yl)-quinoline (2.2 g, 5.62 mmol) in dry pyridine (50 mL). The mixture is stirred for 18 h and concentrated in vacuo. The residue is partitioned between chloroform and saturated sodium chloride. The organic layer is dried (sodium suJfate), filtered, concentrated in vacuo, and the residue chromatographed on S1O2 (dichloromethane to 20% methanol in dichloromethane) to yield the title compound as a red solid, 1.8 g (75%). MS ES+ m/e 424.7 & 426.7 (M+l). A solution of 7-bromo-4-(4 chIoro-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yI)-quinoline (765.0 mg, 1.80 mmol) in 15% (v/v) aqueous Af-methyl pyrrolidinonc (IS mL) is heated at 120 °C for 18 h. The mixture is concentrated in vacuo and the residue chromatographed on SiO2 (dichloromethane to 20% methanol in dichloromethane) to yield a yellow solid, 408.0 mg (60%). MS ES+m/e 406.8 and 408.8 (M+l>. To a solution of 3-(7-bromo-quinolin-4-yl)-2-pyridin-2-yl-5,6-dihydro-4H- pynolo[ 1,2-b]pyrazol-4-ol (89.0 nig, 0.22 mrnol) in dry dichloromethane (2 mL) is added Dess-Martin periodinane (301.0 mg, 0.7] mmol) and the resulting mixture stirred for 18 h. The reaction mixture is chromatographed on SiO2 (dichloromethane to 20% methanol in dichloromethane) to yield a yellow solid, 78 mg (88%). MS ES+m/e 404.7 and 406.7 (M+1). A mixture of 4-(2-pyridin-:2-yl-5,6-dihydro-4H-pyiTolo[ 1,2-b)pyrazol-3-yl)- quinolin-7-ol (1.42 g, 4.30 mmol), 3-fluorobenzontrile (550.0 mg, 4.5 mmol), 18-crown-6 (80.0 mg, 0.37 mmol), and 37%(w/w) potassium fluoride on alumina (3.5 g) in dimethyl sulfoxide (12 mL) are heated at 140 °C for 18 h. The reaction mixture is cooled to room temperature, filtered, and the solics are washed with chloroform. The organic filtrate is washed with brine, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue is chromatographed on S1O2 (dichloromethane to 20% methanol in dichloromethane) to yield a yellow oil. 3-[4-(2-Pyridin-2-yl-5,6-dihydro--tH-pyrrolo[l,2-b]pyrazol-3-yl)-quinolin-7-yloxy]- r benzonitrile; MS ES+m/e 430.1 (M+l). 3-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinolin-7-yloxy]- benzamide; MS ES+m/e447.8 (M+l). Lawasson's Reagent (1.01 g, 2.49 mmol) is added to a solution of Ar,A'-dimethyl- 3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinolin-7-yloxy]- benzamide (0.72 g, 1.51 mmol) in toluene (lOmL). The resulting mixture is heated at 120 °C for 45 min. The mixture is concentrated in vacuo and the residue chromalographed on SiO2 (dichlorc MS ES+m/e 491.8 (M+l). To a refluxing mixture of Raney-nickcl and hydrazine-monohydrate (0.5 mL, 10.17 mmol) in methanol (5 mL) is added MAf-dimethyl-3-[4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrazol-:l-yl)-quinolin-7-yloxy]-thiobenzamide (311.0 mg, 0.63 mmol) in methanol (20 mL). The mixture is stirred 10 min and cooled to room temperature, filtered, and concentrated in vacuo. The residue is chromatographed by HPLC (Cig column) to yield the title compound, 60.2 mg (20%). MS ES+m/e 462.0 (M+l). To a solution of 4-[2-(6-methyI-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l ,2- b]pyrazol-3-yl]-quinoline-l -oxide (103 mg, 0.30 mmol) in TV.jV-dimethylformamide (3 mL) is added trifluoroacetic anhydride (425 ^iL,3.0 mmol). The mixture is stirred for 40 h, poured into water, and the pH adjusted to 8 with saturated aqueous sodium bicarbonate solution. The mixture is extracted three times with ethyl acetate, the combined organic extracts washed three times with water and once with brine, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue is triturated with 10% acetone/90% dichloromethane and filtered. The solid is dried under vacuum to yield the title compound, 11.6 mg (10%), as a yellow solid. TOF MS ES+ exact mass calculated for C23H22CIN4O2 (p+1): m/z = 343.1559. Found: 343.1550. To a solution of 7-methoxy~4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l ,2- b]pyrazol-3-yl)-quinoline (53 mg, 0 16 mmol) in JV.JV-dimethylformamide (3 mL) at room temperature is added sodium ethanthiolate (133 mg, 1.6 mmol). The solution is refluxed for 4 h, cooled, and concentrated in vacuo. The residue is dissolved in methanol and loaded onto an SCX column. The column is washed with water, methanol, and 7 N ammonia in methanol. The appropriate fraction is concentrated in vacuo to yield the title compound, 28 mg (56%), as a yellow solid. TOF MS ES+ exact mass calculated for C2oH|7N40 (p+l): m/z = 329.1402 Found: 329.1413. By the above method the following compounds are prepared (unless otherwise To a mixture of 7-benzyloxy-6-methoxy-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline (17 mg, 0.04 mmol) and 10% palladium on activated carbon (3 mg) in absolute ethanol (2 mL) is added 1,4-cyclohexadkne (100 mg, 1.2 mmol). The mixture is stirred at room temperature for 3 h, treated with methanol (500 |lL), and heated at 60 °C for 3 li. The mixture is cooled, filtered, and loaded onto an SCX column. The column is washed with water, methanol, and 7 N ammonia in methanol. The appropriate fraction is concentrated in vacuo to yield the title compound, 10 mg (77%), as a yellow solid. TOF MS ES* exact mass calculated for C2iH,9N4O2 (p+l): m/z = 359.1508Found: 359. J 520. To a solution of 3-{4-[2-{6-methyl-jjyridJn-2-yl)-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazoI-3-yl]-quinolin-7-yl}-acrylic acid methyl ester (0.041 g, 0.1 mmol)in methanol (1 mL) is added 10% Pd/C (0.1 g). The resulting mixture is placed under one atmosphere of hydrogen and stirred for 18h. The mixture is filtered and concentrated in vacuo. The residue is chromatographed on SiC>2 (2% methanol in dichloromethane) to yield the desired product as a pale yellow solid, 0.035 g (85%). MSAPCf m/e413(M+1). A mixture of 7-bromo-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrro)o(l,2-b]pyrazol-3-yl]-quinoline(1.35 g,, 3.34 mmol), sodium i-butoxide(0.64 g, 6.68 mmol), benzophcnone imine (0.91 g, 5.01 mmol) in toluene (30 mL) is de-gassed with nitrogen for 20 min. To the mixture is added Pd2(dba)3 (0.008 g, 0.008 mmol) and BfNAP (0.012 g, 0.019 mmol), and further de-gassed with nitrogen for 10 min. The mixture is heated at 80 °C for 24 h. Saturated ammonium chloride (30 mL) is added and the mixture extracted with chloroform. The combined organic portions are washed with water and brine, dried (sodium sulfate), and concentrated in vacuo. The residue is taken up in 1:1 methanol/1 N hydrochloric acid (50 mL) and heated at reflux for 2 h. The mixture is concentrated in vacuo and the residue partitioned between saturated sodium bicarbonate and chloroform. The combined organic layers are washed with water and brine, dried (i;odium sulfate), filtered, and concentrated in vacuo. The residue is precipitated from dichloromethane with hexanes (100 mL) and collected by filtration to yield the tith: compound, 1.10 g (96%), as a yellow solid. MSAPCI+m/e342(M+l). To a solution of 3-{4-[2-(6~methyl-pyridin-2-yl)-5,6-dihydro^H-pyjTolo[l,2- b]pyrazol-3-yl]-quinolin-7-yl}-propionic acid methyl ester (0.30 g, 0.73 mmol) and 2M dimethylamine in methanol (1.05 mL, 2.1 mmol) in dichloromethane (1 mL) is added 2 M trimcihylaluminum in hexane (1.64 mL, 3.25 mmol). The solution is healed at 40 °C for 48 h. The mixture is diluted with dichloromethane (150 mL), treated with saturated potassium sodium lartrate (30 mL) and stirred 1S h. The organic portion is separated and washed with water and brine, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue is chromatographed on SiC>2 (10% methanol in dichloromethane) to yield the title compound, 0.29 g (89%), as a yellow foam. MSAPCrm/e426(M+l). To a solution of 3-(4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrro)o[ 1,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-propylamine (25 mg, 0.06 mmol) in pyridine (1 mL) at room temperature is added acetic anhydridt (500 |iL, 5.3 mmol). The mixture is stirred for 2 h, concentrated in vacuo, and the residue chromatographed on S1O2 (89% dichloromethane 10% methanol 1 % concentrated ammonium hydroxide) to yield the title compound ,12 mg (47%), as a light brown solid TOF MS ES+ exact mass calculated for C25H26N5O2 (p+1): m/z = 428.2086. Found: 428.2095. Neat 1 -(1 -aza-2-pyridin-2-yl-3-quiiiolin-4-yl-prop-1 -enyl)piperidine-2,6-dione (0.64 g, 1.8 mmol) is heated at 180 °C for 2 h. After cooling, the residue is allowed to cool, dissolved in dichloromethane (15 mL), cooled to -70 °C, and treated with a 1.0 M solution of D1BAL-H in toluene (1.9 mL, 1.9 mmol) dropwise. The mixture is stirred for 0.S h, the cold bath removed, and stirred for an additional 18 h. The reaction is diluted with saturated aqueous ammoniom chloride solution. The mixture is partitioned between ethyl acetate and water. The organic portion is washed with water and brine, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue is precipitated from ethyl acetate with hexane to yidd title compound, 0.S8 g (62%), as a white solid. TOF MS ES+ exact mass calculated for C2|H|8N4O (p+1): m/z = 343.1559. Found: 343.1570. A solution of 2-pyridin-2-yl-3-quinolin-4-yl-pyrazolo[l,5-a]piperidin-7-ol (0.04 g, 0. ] 2 mmol) and acetic anhydride (0.2 mL) in pyridine (2 mL) at room temperature is stirred for 24 h. The mixture is partitioned between ethyl acetate and water. The organic portion is washed with water and brine, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue is chromatographed on S1O2 (5% methanol/dichloromethane) to yield the title compound, 0.41 g (91%), as a white solid. TOF MS ES+ exact mass calculated for C23H21N4O2 (p+1): m/z = 385.1665. Found: 385.1668. A solution of methyl-{3-(4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo{l,2-b]pyrazol- 3-yl)-quinolin-7-yloxy]-propyl}-carbamic acid tert-butyl ester (100 mg, 0.2 mmol) in trifluoracetic acid (3 mL) is stirred at room temperature for 6 h. The mixture is concentrated in vacuo and traces of trifluoroacetic acid removed by repeated evaporation with chloroform. The residue is placed on an SCX column and washed with water, methanol, and 7 N ammonia in methanol. Concentration of the appropriate fraction yields the title compound, 40 mg (50%), as yellow oil. MSES+m/e400(M+l). A solution of 3-(4-fluoro-phenyl)-2-«>-methyl-1 -oxy-pyridin-2-yl)-5,6-dihydro- 4H-pyrrolo[l,2-b]pyrazole (82 rag, 0.27 mmol) in chloroform (2 mL) is treated with excess trifluoroacetic anhydride aind warmed at reflux for 2 h then concentrated in vacuo. The residue is treated with excess; solid potassium carbonate in methano! at reflux for 30 min. The mixture is concentrated, then partitioned between ethyl acetate and water. The ethyl acetate portion is concentrated and the residue purified on a silica cartridge (10% pyridine ethyl acetate) to yield 24 mg (29%) of the title compound as a yellow foam. MS,Erm/e310(M+l). To a solution of 6-(3-quinolin-4-yl-5,6-dihydro-4H-pyrrolo(l,2-b]pyrazol-2- yl)pyridine-2-carboxylic acid meithyl ester (0.550 g, 1.48 mmol) in methanol (20 mL) is added lithium borohydride (35.5 img, 1.63 mmol). The mixture is stirred lh, additional lithium borohydride (35.5 mg, 1.63 mmol) added, and the resulting mixture stirred at room temperature for 16 h. 4 N Hydrochloric acid (3 mL) is added slowly and the resulting mixture concentrated in vacuo. The residue is taken up in methanol (10 mL) and partitioned between ethyl acetate (150 mL) and saturated potassium carbonate (150 mL). The organic portion is washed with brine (150 mL), dried (magnesium sulfate), and concentrated in vacuo. The residue is precipitated from ethyl acetate with hexanes to yield 296 mg (58%) of the title compound. MSES+m/e342(M+l). To a solution of 3-(4-roethoxy-phenyl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-bJpyrazole (72 mg, 0.24 mmol) in methylene chloride (1 mL) is added boron tribromide (0.3 mL). The solution is stirred at ambient temperature for 3 h, then quenched with methanol. The mixture is concentrated in vacuo to a reddish solid. The solid is passed through a silica gel cartridge (methylene chloride, ethyl acetate, then acetone). The appropriate methylene chloride fractions are concentrated in vacuo to yield 4 mg (5.8%) of the title compound. The more polar fractions are concentrated in vacuo then treated with aqueous ammonium chloride and methanol. The mixture is concentrated in vacuo and the residue purified on a silica cartridge eluting as above. Appropriate fractions are combined and concentrated in vacuo to yield an additional 49 mg (71%) of the title compound. MSES+m/z292(M+l). To a 1 M solution of lithium aluminum hydride in letrahydrofuran (0.60 mL, 0.59 mmol) is added a solution of 3-[4H2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yl)-quinolin-7-yloxymethyl]-pyrrolidine-l -carboxylic acid benzyl ester (215 mg, 0.39 mmol) in tetrahydrofuran (2 mL). The mixture is heated at 65 °C for 2 h, cooled to 0 °C, and diluted with saturated aqueous sodium potassium tartrate solution. The mixture is extracted with chloroform and the organic portion chromatographed on SiOj to yield the title compound, 112 mg (67%), as a yellow foam. MS APC+m/e426(M+l). A mixture of 4-[2-(6-niethyl-pyridin-2-yl)-5,6-dihydro-4H-pyrroIo[l,2-b]pyrazoI- 3-yI]-quinoline-7-carboxy1ic acid (2-amino-l,l-dimethyl-ethyl)-amide (0.12 g, 0.27 mmol), sodium cyanoborohydridt: (0.038 gv 0-6 mmol), and acetic acid (0.077 ml, 1.3 mmol) in methanol (5 mL) is cooled to 0 °C and stirred for 10 min. A solution of 37% aqueous formaldehyde (0.086 ml., 3.1 mmol) in methanol (2 mL) is added dropwise. The mixture is allowed to warm to room temperature and stirred for 1 h. The reaction is quenched with saturated aqueous potassium carbonate solution and concentrated in vacuo. The residue is taken up in chloroform, washed with water and brine, dried (sodium sulfate) and concentrated in vacuo. The residue is chromatographcd on SiOz (8% methanoI/92% dichloromethane) to yield the title compound, 33 mg (27%), as a white foam. MS APC* m/e 504 (M+l). To a solution of (S)-6-ben2yloxymclhyl-3-(4-fluoro-phenyl)-2-(6-methyl-pyridin- 2-yl)-5,6-dihydro-4H-pyiToJo[l,2-b]pyra2ole (0.3 g, 0.73 mmol) in chloroform (1.0 mL) is added trimethylsilyl iodide (0.173 mL, 1.21 mmol). The mixture is stirred 2 h, diluted with methanol (10 mL), stirred 10 rain, and concentrated in vacuo. The residue is taken up in ethyl acetate (50 mL), washed with aqueous sodium thiosulfate (2 X 50 mL), saturated sodium bicarbonate solution, and brine. The resulting solution is dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue is chromatographed on S1O2 (3% methanol/ethyl acetate) to yield the title compound, 149 mg (64%), as a pale yellow solid. MS APC1* m/e324 (M+l); melting range: 142-144°C. A mixture of potassium cyanide (44 mg, 0.67 mmol), tetrabutylammonium iodide (catalytic), and (S)-methanesulfonic acid 3-(4-fluoro-phenyl)-2-(6-methyl-pyridin-2-yl)- 5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-6-ylmethyl ester (54 mg, 0.135 mmol) in N,N- dimethylformamidc (0.35 mL) and water (0.13 mL) is heated at 70 °C for 4 h. The mixture is cooled, taken up in ethyl acetate (20 mL), washed with water and brine, dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue is chromatographed on SiO2 (2% methanol/chloroform) to yield the title compound, 25 mg (56%). MS APCI+ m/e 333 (M+1). To a solution of (0.230 g, 1 nimol) of 4-(2-(2-pyridy))ethynyl)quinoline in xylene (2mL) is added 3a H-pyrrolidino[l,2-C] l,2,3-oxadiazolin-3-one (0.252 g, 2 mmol) and the resulting solution heated in an oil bath at reflux under argon for 48 h, concentrated in vacuo, and the residue chromatographed on SiO2 (0 to 1 % methanol in chloroform with 3 drops ammonium hydroxide per 150 mL solvent) to yield 18 mg of title compound as an oil. MSES+m/e3l3(M+l). To a solution of 5-pyridin-2-yl-4-quinolin-4-yl 2H-pyrazol-3-ol (50 mg, 0.17 mmol), ethylene glycol (15 mg, 0.24 mmol) and tri-n-butylphosphine (100 mg, 0.50 mmol) in tetrahydrofuran (15 mL) is added 1,1 *-(azodicarbonyl)dipiperidine (120 mg, 0.48 mmol). The solution is heated at reflux for 5 h, cooled, and filtered through an SCX cartridge. The residue is chromatographed on SiO2(15:l dichloromethane:methanol). The product residue is converted to the disoxylate salt to give the title compound 40 mg (46%). 'H NMR (CDCb): 6 8.81 (d, J - 4 Hz, 1H), 8.42 (m, 1H), 8.11 (d, J = 8 Hz, 1H), 7.83 (d, J = 8 Hz, 1H), 7.65 (ddd, J = 8,7, Hz, 1H), 7.46 (ddd, J = 8,7, J Hz, 1H), 7.38 (ddd, J = 8, 7,1 Hz, IH) 7.24-7.29 (m, 2H), 7.O6-7.IO(m, 1H); MS ES+ m/e 315.0 (M+l). TOF MS ES+ exact mass calculated for CH,jN40 (p+1): m/z= 315.1246. Found: 315.1248. To a solution of [4-(2-py)idin-2-yl-5,6-dihydro-4H-pyrTolo[l,2-b]pyrazol-3-yl)- quinolin-7-yl]-carbamic acid 2-hydroxy-ethyI ester (40.2 mg, 0.097 mmol) and triphcnylphosphine (35.0 mg, 0.14 mmol) in tetrahydrofuran (1 mL) at room temperature is added diethyl 40% azodicartmylate in toluene (50 uL, 0.11 mmol). The mixture is stirred 18 h, filtered, and the filtrate concentrated in vacuo. The residue is chromatographed on SiO2 (2% to 15% methanol in dichloromethane) to yield the desired product, 15.2 mg (40%). MS ES+m/e 398.0 (M+l). 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazoI-3-yl)-quinolin-7-ol (0.100 g, 0.305 mmol), triphenylphosphine (0.080 g, 0.305 mmol), and 4-pyridylcarbinoJ (0.033 g, 0.305 mmol) are combined in toluene (1.0 mL) and treated with diisopropylazodicarboxylate (0.062 g, 0.305 mmol). The resulting mixture is heated at 75 °C for 18 hours. The mixture is diluted with tetrahydrofuran and heated at 75 °C for 24 h. The mixture is placed on a 10 g SiCX resin column which is washed sequentially with dichtoromethane (120 mL), methanol (60 mL), and 4:1 dichloromethane/2 N ammonia in methanol (125 mL). The latter fraction is concentrated in vacuo and the residue chromatographed on SiC>2 (9:1 ethyl acetate:2N ammonia in melhanol) to yield the desired product as a tan solid, 0.035 g (27%). MSES' m/e 420 (M+l). Ethylenediame (45 mL, 0.67 mmol) is added dropwise to a stirred solution of 2.0 M trimethylaluminum in toluene (0.5 mL, 1.0 mmol) and 4-(2-pyridin-2-yl-5,6-dihydro- 4//-pyTTolo[l,2-b]pyrazol-3-yl)-quinoline-6-carboxylic acid methyl ester (250.0 mg, 0.675 mmol) at 0 °C. The mixture is warmed to room temperature, then refluxed for 3 h. The solution is cooled and diluted with water (0.5 mL) and methanol (1 mL). The mixture is refluxed for 10 min, cooled, filtered, extracted into chloroform, and the organic portion washed with brine. The organic layer is concentrated in vacuo and the residue is chromatographed on SiO2 (10% to 30% methanol in dichloromethane) to yield the title compound, 46 mg (18%), as an yellow oil. MS ES'm/e 381.0 (M+l). Racemic4-[5-(4-nuoro-plicnyl)-2-(6-methyl-pyridin-2-yl)-5,6-dihychro-4H- pyrrolo[l,2-b]pyrazoI-3-yl]-quinoline (1 JO mg, 0.26 mmol) is separated into pure enantiomers by preparative HPLC with a Chiralcel OD (50X500mm) column (25:75 isopropanol/heptane and detector at 220 nm). Fractions containing the first eluting compound are combined and concentrated to yield the title compound, 44 mg (40%), as an off-white foam. 'H NMR (CDC13): 5 8.85 (d, J = 4.5 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.65 (td, J = 1.5, 8 Hz, IH), 7.35 (td, J = 1.5, 8 Hz, 1H), 7.20-7.30 (m, 4H), 6.85-7.10(m,4H), 4.80 (dd,J = 8.4,11 Hz, IH), 4.35 (dd, J = 7, 11 Hz, 1H), 4.15-4.25 (m, IH), 3.30 (dd, J = 8.4, 16 Hi, IH), 2.85 (dd, J = 6, 16 Hz, IH), 2.30 (s, 3H). MS APC1+ m/e421 (M+l). Racemic4-[5-(4-fluoro-pbmyl>2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yI]-quinolime (110 ing, 0.26 mmol) is separated into pure enantiomers by preparative HPLC with a Chiralcel OD (50X500mm) column (25:75 isopropanol/hepiane and detector al 220 nm). Fractions containing the second eluting compound are combined and concentrated to give the title compound, 59 mg(54%), as an off-white foam. 'H NMR (CDC1,): 5 8.85 (d, J = 4.5 Hz, 1H), 8. JO (d, J = 8.4 Hz, 1H), 7.80 (d, J - 8.4 Hz, 1H), 7.65 (td, J = 1.5, 8 Hz, 1H), 7.35 (td, J=1.5,8 Hz, 1H), 7.20-7.30 (m, 4H), 6.85- 7.10 (m, 4H), 4.80 (dd, J = 8.4, 11 Hz, 1H), 4.35 (dd, J - 7,11 Hz, 1H), 4.15-4.25 (m, 1H), 3.30 (dd, 3 - 8.4,16 Hz, 1H), 2.85 (dd, J = 6,16 Hz, 1H), 2.30 (s, 3H). MSAPCl+m/e421 (M+l). Add tributylvinyltin (0.0S9mL, 0.19mmol) to a solution of 4-[2-(6-chioro-pynain- 2-yl)-5,6-dihydro-4H-pyrrolo[U-bi>yrazol-3-yl)-quinoline, EXAMPLE 101, (59 mg, 0.17mmol) in toluene (0.7mL) atRT. Bubble nitrogen into the reaction mixture for 5min and add tetrakis-(triphenylphospi«te) palladium (0) (10 mg, 0.0085mmol). Bubble nitrogen into the solution for an additional 2min and heat the reaction to 1 lOoC for 18h. Concentrate the reaction in vacuo and purify by flash column chromatography (SiO2,20- 40% acetone/hexanes) to provide the title compound (35 mg, 62%) as a white solid. MS Calcd. 338; MS (APC1) (M-^l) 339. Dissolve 3-{4-{2-(6-methyl-pyridin-2-y1)-5'6-dinydro"4H'pyrrolo[ ' b]pyrazol-3-ylJ-quinolin-6-yl}-aciyIic acid methyl ester (0.040 g, 0.1 mmol) in methanol/water (3:1,2 mL). Acid lithium hydroxide (0.010 g, 0.25 mmol) and stir the mixture 18 h. Remove the solvait then load the residue on a SCX resin column with methanol. Elute the column with methanol (50 mL) then with 2 N ammonia/methanol to give the desired product as a pale yellow solid 0.036 g (92%) MS APCI" m/e 397 (M+l). The compounds disclosed herein were tested by the following protocols for TGF- P inhibition, as described below in the protocol description. The data collected thereby is shown below. TGF-B RECEPTOR I AiND 11 PURIFICATION AND IN VITRO K1NASE REACTIONS For TGF-p" Type I (RIT204D) and Type II (RI1 WT) Receptors: The 6X-H1S tagged cytoplasmic kimase domain of each receptor was expressed and purified from Sf9 insect cell lysates as briefly described below: Cell pellets after 48-72 hrs of infection were lysed in lysis buffer (LB: 50 mM Tris pH 7.5, 150 mM NaCl, 50 mM NaF, 0.5% NP40 with freshly added 20 mM p1- mercaptoethanol, 10 mM imidazole, 1 mM PMSF, IX EDTA-frce Complete Protease lnhibitor(Boehringer Mannheim). Cell lysates were clarified by centrifugation and 045 uM filtered prior to purification by Ni/NTA affinity chromatography (Qiagen). Chromatography Protocol: Equilibrate with 10 CV of LB, load sample, wash with 10 CV RIPA buffer (50 mM Tris pH 7.5, 150 mM NaCl, 1% NP40, lmM EDTA, 0.25% sodium deoxycholate, added fresh 20 mM p-mercaptoethanol, 1 mM PMSF), wash with 10 CV LB, wash with 10 CV IX KB (50 mM Tris pH 7.5, 150 mM NaCl, 4 mM MgCI2, 1 mM NaF, 2 mM p*- mercaptoethanol), eiute with a linear gradient of IX KB containing 200 mM lmidazole. Both enzymes were approximately 90% pure and had autophosphorylation activity. Reactions: 170-200 nM enzyme in IX KB, compound dilution series in IX KB/16% DMSO (20 uM to 1 nM final concentration with 4% OMSO final concentration), reactions started by adding ATP mix (4 uM ATP/I uCi 33P-D-ATP final concentrations) in IX KB. Reactions were incubated at SO °C for 1 hr RIT204D or 40 min for R1I WT. Reactions were stopped and quantitated using standard TCA/BSA precipitation onto Millipore FB glass fiber filter plates and by liquid scintillation counting on a MicroBeta JET. Representative data for compounds of the current invention with the RIT204D 1C50 MV1LU P3TP-LUX ASSAY A stable MvlLu clone (Ci) containing the p3TP-Lux reporter was created by standard transfection and puromycin selection protocols. This stable clone was used to screen the example compounds for their ability to inhibit TGF-p dependent luciferase production as briefly described below: 1. Plated Mv 1 Lu C1 cells in Wallac™ Black Isoplates 2. Allowed cells to adhere overnight. 3. Removed media and replaced with 0.5% FBS DMEM media 4. Added the compound dilution series in 0.5% FBS/DMEM containing 1% DMSO such that the final compound concentration ranged from 20 uM to 0.1 nM and the final DMSO concentration was 0.2%. 5. Incubated at 37°C/5% CO2 for 2 hrs. 6. Added 0.5% FBS/DMEM as control or TGF-pl diluted - in 0.5% FBS/DMEM (final concentration of 10 pM) to the -/+ TGF-{3 wells respectively 7. Incubated for 16-20 hrs. at 37°C/5% CO2 8. Removed media and rinsed IX with PBS. 9. Removed PBS and lysed the cells with IX Passive Lysis Buffer (Promega) at room temperature. 10. Counted relative luciferase activity on the MicroBeta JET by injecting Luciferase Assay Reagent 11 (PROMEGA). The use of the above assay in measuring TGF-ji responsive activity is described in Wrana.etal. CeH71: 1003-1014(1992). Representative data for compounds of the current invention with the p3TP-LUX 1C50 p38otlN VITRO KINASE ASSAY Active p38a/SAPK2a w»s purchased from Upstate Biotechnology (cat#l4-251). A known p38oc substrate from EGFR was used in the assay (Young, et al. (1997) JBC 272:12116-12121). Reactions were performed in IX kinase buffer (25 mM Tris-HCl pH 7.5, 5 mM p- glycerophosphate, 2 mM DTT,0.1 mM Na3VO4, 10 mM MgCl2, 1 uM Microcystin) with 5 nM p38a, 62.5 uM substrate, 40 uM to 0.2 nM compound dilution series in IX KB/16% DMSO (final 4% DMSO concentration). Reactions were started by addition of 100 uM ATP (final concentration) with 1 uCi "P-y-ATP in IX KB and incubated at 30°C for 40 min. Reactions were stopped with HjPO4 and quantitated on Millipore PH phosphocellulose filter plates by liquid scintillation counting on a MicroBeta JET. Representative data for compounds of the current invention with the p38a IC50 KDR fVEGFR2) PURIFICATION AND IN VITRO K1NASE ASSAY The 6X-H1S tagged cytopJasmic kinase domain of KDR was expressed and purified from Sf9 insect cell lysates as described above with the following modification: IX kinase buffer for chroraiatography washes and elution was changed to 100 mM HEPES pH 7.5, ] 0 mM MnCl2 and 5 mM P-mercaptoethanol. The resulting material was approximately 40% pure and had tyrosine autophosphorylation activity. Reactions: 1 ug enzyme in IX KB, compound dilution series in IX KB/16% DMSO (20 uM to I nM final concentration with 4% DMSO final concentration), reactions were started by adding ATP mix (1 uM ATP/1 uCi 33P-D-ATP final concentrations) in IX KB. Reactions were incubated at 30°C for 20 min. The reactions were stopped and quantitated using standard TCA/BSA precipitation onto Millipore FC glass fiber filter plates and by liquid scintillation counting on a MicroBeta JET. Representative data for compounds of the current invention with the KDR ICS0 Conditions "characterized by enhanced TGF-P activity" include those wherein TGF-P synthesis is stimulated so that TGF-P is present at increased levels or wherein TGF-P latent protein is undesirably activated or converted to active TGF-P protein or wherein TGF-P receptors are uprcgulated or wherein the TGF-P protein shows enhanced binding to cells or extracellular matrix in the location of the disease. Thus, in either case "enhanced activity" refers to any condition wherein the biological activity of TGF-p is undesirably high, regardless of the cause. A number of diseases haw been associated with TGF-p 1 over production. Inhibitors of TGF-B intracellular signaling pathway are useful treatments for fibroproliferative diseases. Specifically, fibroproliferative diseases include kidney disorders associated with unregulated TGF- 0 activity and excessive fibrosis including glomerulonephritis (GN), such as nesangial proliferative GN, immune GN, and crescentic GN. Other renal conditions include diabetic nephropathy, renal interstitial fibrosis, renal fibrosis in transplant patients receiving cyclosporin, and HIV-associated nephropathy. Collagen vascular disorders include progressive systemic sclerosis, polymyositis, scleroderma, dermatomyositis, eosinophilic fascitis, morphea, or those associated with the occurrence of Raynaud's syndrome. Lung fibroses resulting from excessive TGF- B activity include adult respiratory distress syndrome, idiopathic pulmonary fibrosis, and interstitial pulmonary fibrosis often associated with autoimmune disorders, such as systemic lupus erythematosus and scleroderma, chemical contact, or allergies. Another autoimmune disorder associated with fibroproliferative characteristics is rheumatoid arthritis. Eye diseases associated with a fibroproliferative condition include retinal reattachment surgery accompanying proliferative vitreoretinopathy, cataract extraction with intraocular lens implantation, and post glaucoma drainage surgery are associated with TGF-P 1 overproduction. Fibrotic diseases associated with TGF-|3l overproduction can be divided into chronic conditions such as fibrosis of the kidney, lung and liver and more acute conditions such as dermal scarring and restenosis (Chamberlain, J. Cardiovascular Drug Reviews, J9(4):329-344). Synthesis and secretion of TGF-pi by tumor cells can also lead to immune suppression such as seen in patients with aggressive brain or breast tumors (Arteaga, et al. (1993) J. Oin. Invest. 92:2569-2576). The course of Leishmanial infection in mice is drastically altered by TGF-pl (Barral-Netto, et al. (1992) Science 257:545-547). TGF-pl exacerbated the disease, whereas TGF-pM antibodies halted the progression of the disease in genetically susceptible mice. Genetically resistant mice became susceptible to Leishmanial infection upon administration of TGF-pM. The profound effects of TGF-fJl on extracellular matrix deposition have been reviewed (Rocco and Ziyadeh (1991) in Contemporary Issues in Nephrology v.23, Hormones, autocoids and the kidney, ed. Jay Stein, Churchill Livingston, New York pp.391-410; Roberts, et al. (1988) Rec. Prog. Hormone Res. 44:157-197) and include the stimulation of the synthesis and the inhibition of degradation of extracellular matrix components. Since the structure and filtration properties of the glomerulus are largely determined by the extracellular matrix composition of the mesangium and glomerular membrane, it is not surprising that TGF-Pl has profound effects on the kidney. The accumulation of mesangial matrix in proliferative glomerulonephritis (Border, et al. (1990) Kidney Int. 37:689-695) and diabetic nephropathy (Mauer, et al. (1984) J. Clin. Invest. 74:1143-1155) are clear and dominant pathological features of the diseases. TGF- PI levels are elevated in human diabetic glomerulosclerosis (advanced neuropathy) (Yamamoto, et al. (1993) Proc.Nati.Acad. Sci. 90:1814-1818). TGF-pl is an important mediator in the genesis of renal fibrosis in a number of animal models (Phan, et al. (1990) Kidney Int. 37:426; Okuda, et al. (1990) J. Clin. Invest. 86:453). Suppression of experimentally induced glomerulonephritis in rats has been demonstrated by antiserum against TGF-fJl (Border, et al. (1990) Nature 346:371) and by an extracellular matrix protein, decorin, which can bindTGF-|Jl (Border, et al. (1992) Nature 360:361-363). Too much TGF-p*l leads to dermal scar-tissue formation. Neutralizing TGF-pl antibodies injected into the margins of healing wounds in rats have been shown to inhibit scarring without interfering with the rate of wound healing or the tensile strength of the wound (Shah, et al. (1992) Lancet 339:213-214). At the same time there was reduced angiogenesis, reduced number of macrophages and monocytes in the wound, and a reduced amount of disorganized collagen fiber deposition in the scar tissue. TGF-pl may be a factor in he progressive thickening of the arterial wall which results from the proliferation of smooth muscle cells and deposition of extracellular matrix in the artery after balloon angioplasty. The diameter of the restenosed artery may be reduced 90% by this thickening, and since most of the reduction in diameter is due to extracellular matrix rather than smooth muscle cell bodies, it may be possible to open these vessels to 50% simply by reducing extensive extracellular matrix deposition. In uninjured pig arteries transfected in vivo with a TGF-01 gene, TGF-p*l gene expression was associated with both extracellular matrix synthesis and hyperplasia (Nabel, et al. (1993) Proc. Natl. Acad. Sci. USA «>0:10759-10763). The TGF-J31 induced hyperplasia was not as extensive as that induced with PDGF-BB, but the extracellular matrix was more extensive with TGF-Pl transfectants. No extracellular matrix deposition was associated with FGF-1 (a secreted form of FGF) induced hyperplasia in this gene transfer pig model (Nabel (1993) Nature 362:844-846). There are several types of cancer where TGF-pi produced by the tumor may be deleterious. MATLyLu rat prostate cancer cells (Steiner and Barrack (1992) Mol. Endocrinol 6:15-25) and MCF-7 human breast cancer cells (Arteaga, et al. (1993) Cell Growth and Differ. 4:193-201) became more tumorigenic and metastatic after transfection with a vector expressing the mouse TGF-pi. TGF-p* 1 has been associated » with angiogenesis, metastasis and poor prognosis in human prostate and advanced gastric cancer (Wikstrom, P., et al. (1998) Prostate 37: 19-29; Saito, H. et al. (1999) Cancer 86: 1455-1462). Jn breast cancer, poor prognosis is associated with elevated TGF-p* (Diclcson, et al. (1987) Proc. Natl. Acad. Sci. USA 84:837-841; Kasid, et al. (1987) Cancer Res. 47:5733-5738; Daly, et al. (1990) J. Cell Biochem. 43:199-211; Barrett-Lee, et al. (1990) Br. J Cancer 61:612-617; King, et al. (1989) J. Steroid Biochem. 34:133-138; Welch, et al. (1990) Proc. Natl. Acad. Sci. USA 87:7678-7682; Walker, et al. (1992) Eur. J. Cancer 238:641-644) and induction of TGF-p*l by tamoxifen treatment (Butta, et al. (1992) Cancer Res. 52:4261-4264) has been associated with failure of tamoxifen treatment for breast cancer (Thompson, et al. (1991) Br. J. Cancer 63:609-614). Ami TGF-P 1 antibodies inhibit the growth of MDA-231 human breast cancer cells in athymic mice (Arteaga, et al. (1993) J. Clin. Invest. 92:2569-2576), a treatment which is correlated with an increase in spleen natural killer cell activity. CHO cells transfected with latent TGF-P 1 also showed decreased NK activity and increased tumor growth in nude mice (Wallick, et al. (1990) J. Exp. Mcd. 172:1777-1784). Thus, TGF-P secreted by breast tumors may cause an endocrine immune suppression. High plasma concentrations of TGF-P 1 have been shown to indicate poor prognosis for advanced breast cancer patients (Anscher, et al. (1993) N. Engl. J. Med. 328:1592-1598). Patients with high circulating TGF-P before high dose chemotherapy and autologous bone marrow transplantation are at high risk for hepatic veno-occlusive disease (15-50% of all patients with a mortality rate up to 50%) and idiopathic interstitial pneumonitis (40-60% of all patients). The implication of these findings is 1) that elevated plasma levels of TGF-p*1 can be used to identify at risk patients and 2) that reduction of TGF-P 1 could decrease the morbidity and mortality of these common treatments for breast cancer patients. Many malignant cells secrete transforming growth factor-P (TGF-p), a potent immunosuppressant, suggesting than TGF-P production may represent a significant tumor escape mechanism from host immunosurvcillance. Establishment of a leukocyte sub- population with disrupted TGF-P signaling in the tumor-bearing host offers a potential means for immunotherapy of cancel. A transgenic animal model with disrupted TGF-P signaling in T cells is capable of eradicating a normally lethal TGF-P overexpressing lymphoma tumor, EL4 (Gorelik and Flavell, (2001) Nature Medicine 7(10): 1118-1122). Down regulation of TGF-P secretion in tumor cells results in restoration of immunogenicity in the host, while 1 -cell insensitivity to TGF-P results in accelerated differentiation and autoimmunity, elements of which may be required in order to combat self-antigen-expressing tumors in a (olerized host. The immunosuppressive effects of TGF-p have also been implicated in a subpopulation of HIV patients with lower than predicted immune response based on their CD4/CD8 T cell counts (Garba, et al. J. Immunology (2002) 168: 2247-2254). A TGF-p neutralizing antibody was capable of reversing the effect in culture, indicating that TGF-P signaling inhibitors may have utility in reversing the immune suppression present in this subset of HIV patients. During the earliest stages ofcarcinogenesis, TGF-pi can act as a potent tumor suppressor and may mediate the actions of some chemopreventive agents. However, at some point during the development and progression of malignant neoplasms, tumor cells appear to escape from TGF-P-depeifident growth inhibition in parallel with the appearance of bioactive TGF-P in the microenvironment. The dual tumor suppression/tumor promotion roles of TGF-p have been most clearly elucidated in a transgenic system overexpressing TGF-P in keratinocytes. While the transgenics were more resisitant to formation of benign skin lesions, the rate of metastatic conversion in the transgenics was dramatically increased (Cui, et al (1996) Cell 86(4):531 -42). The production of TGF-p 1 by malignant cells in primary tumors appears to increase with advancing stages of tumor progression. Studies in many of the major epithelial cancers suggest that the increased production of TGF-P by human cancers occurs as a relatively late event during tumor progression. Further, this tumor-associated TGF-P provides the tumor cells with a selective advantage and promotes tumor progression. The effects of TGF-P on cell/cell and cell/stroma interactions result in a greater propensity for invasion and metastasis. Tumor-associated TGF-p may allow tumor cells to escape from immune surveillance since it is a potent inhibitor of the clonal expansion of activated lymphocytes. TGF-P has also been shown to inhibit the production of angiostatin. Cancer therapeutic modalities such as radiation therapy and chemotherapy induce the production of activated TGF-P in the tumor, thereby selecting outgrowth of malignant cells that are resistant to TGF-p growth inhibitory effects. Thus, these anticancer treatments increase the risk and hasten the development of tumors with enhanced growth and invasiveness. In this situation, agents targeting TGF-p-mediated signal transduction might be a very effective therapeutic strategy. The resistance of tumor cells to TGF-P has been shown to negate much of the cytotoxic effects of radiation therapy and chemotherapy and the treatment- dependent activation of TGF-P in the stroma may even be detrimental as it can make the microenvironment more conducive to tumor progression and contributes to tissue damage leading to fibrosis. The development of a TGF-P signal transduction inhibitors is likely to benefit the treatment of progressed cancer alone and in combination with other therapies. be administered and the choice of route of administration and therefore the above preferred dosage range is not intended to limit the scope of the present invention in any way. The formulations useful for separate administration of the TGF-p* antagonists will normally consist of at least one compound selected from the compounds specified herein mixed with a carrier, or diluted by a carrier, or enclosed or encapsulated by an ingestible carrier in the form of a capsule, sachet, cachet, paper or other container or by a disposable container such as an ampoule. A carrier or diluent may be a solid, semi-solid or liquid material which serves as a vehicle, excipient or medium for the active therapeutic substance. Some examples of the diluents or carrier which may be employed in the pharmaceutical compositions of the present invention are lactose, dextrose, sucrose, sorbitol, mannitol, propylene glycol, liquid paraffin, white soft paraffin, kaolin, fumed silicon dioxide, microcrystalline cellulose, calcium silicate, silica, polyvinylpyrrolidone, cetostearyl alcohol, starch, modified starches, gun acacia, calcium phosphate, cocoa butter, ethoxylated esters, oil of theobroma, arachis oil, alginates, tragacanth, gelatin, syrup, methyl cellulose, polyoxyethylene sorbitan monolaurate, ethyl lactate, methyl and propyl hydroxybenzoate, sorbitan trioleate, sorbitan sesquioleate and oleyl alcohol and propel Ian ts such as trichloromonofluoromethane, dichlorodifluoromethane and dichlorotetrafluoroethane. In the case of tablets, a lubricant may be incorporated to prevent sticking and binding of the powdered ingredients in the dies and on the punch of the tableting machine. For such purpose there may be employed for instance aluminum, magnesium or calcium stearates,tele or mineral oil. Preferred pharmaceutical forms of the present invention are capsules, tablets, suppositories, injectable solutions, creams and ointments. Especially preferred are formulations for inhalation application, such as an aerosol, for injection, and for oral ingestion. trifluoromethyl, halo, trifluoromethoxy, hydroxymethyl, N-pyrrolidino, N-morpholino, phenylthio, (Cl-C4)dialkylaminomelhyl, methoxyphenyl, amino, hydroxy, carboxyl, phenyl, arylalky; R2 is unsubstituted or substituted quinolinc; unsbustitutcd OR.substituted quinoline N-oxide; unsbustituted or substituted phenyl; unsubstituted or substituted naphthalene; r unsubstituted or substituted pyridine; unsubstituted or substituted pyridine N-oxide; unsbustituted or substituted quinazoline; unsubstituted or substituted cinholine; unsubstituted or substituted benzodioxole; unsbustituted or substituted benzodioxane; unsubstituted or substituted pyrimid ne; unsubstituted or substituted benzothiophene; or unsubstituted or substituted phenantforolene; wherein the substitution may independently be one or more of the following: hydrogen, (Cl-C6)alkyl, (C2-C6)alkenyl, (C2- C6)alkynyl, (C1-C6) alkylhalide, (C 1-C6)alkoxy, (C2-C6)alkenyloxy, (C2- C6)alkynyloxy, (Cl-C6)alkylthio, (Cl-C6)alkylsulphinyl, (Cl-C6)alkylsulphonyl, (Cl- C6>lkylamino, di-((Cl -C6)alkyl)ainino, (C! -C6)alkoxycarbonyl, N-(C 1 - C6)alkylcarbamoyl, N,N-di-((Cl-C5)aIkyl]carbamoyl, aminooxy, N-(C 1 -C6)alkyl aminooxy, N,N-di-((Cl-C6)alkyl]aminooxy, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino,N-(Cl-C6)alkyl-(C2-C6)alkanoylamino, (C3.C6)alkenoylamino, N-(C1-C6)alkyl-(C3-C6)alkenoylarnino, (C3-C6)alkynoylamino, N-(C1 -C6)alkyl-(C3- C6)alkynoylamino, sulphamoyl,N.(Cl-C6)alkylsulphamoyl, N,N-di-((Cl- C6)alkyl}sulphamoyl,(Cl-C6)a1kanesulphonylaniino,N-(Cl-C6)alkyl.(Cl- C6)alkanesulphonylamino, carboxumide, ethylene, phenyl, thiophenyl, aminophenyl, phenylthio, halo, cyano, pyridinyl, arylalkyl, hydroxy, N-pyrrolidino, N-morpholino, carboxyl, (5>phenyM,2,4-oxadiazole-3-yl]methoxy, 6-methyl-pyridazin-3-yloxy, (5-oxo- 2-pyrrolidinyl)methoxy, 2-(4,5-dihydro-lH-imidazolyl),N, N-dialkylcarbamoyloxy, 1- hydroxy-1-methylethyl, 4-fluorophenyl, 3,4-rnethylenedioxyphenyl, trifluoromethyl, trifluoromethoxy, wherein: X| is 0, N, S, SO^NRu, 0(0), or bond; Q( is hydrogen, phenyl, 5- difluoro-1,3-benzodioxolyl), C(OXJs> or pyridyl when, except when one is 0 the other cannot be 0 are independently 0-2; Qi is ORn, NR11R12, halo, N-morpholino, N- pipcrazino-N'R, j, N-imidazolyl, N pyrazolyl, N-triazolyi, N-(4-pipcridinylpiperidine), SO2R14, SORM, NHSO2R15, acetamido, N-phthalimido, N-oxazolidino, N-imidazolino, N- benzoxazolidino, N-pyrolidinonyl, N(N'-mcthylbenzimidazolino), N,N-di(CI- C4)alkylamino(Cl-C4)alkoxy, N-benzimidazolino; when m and n are independently 0-2, but one or the other of m or n is not 0; Q} is hydroxy, methoxy, amino, diethylamino, dimcthylamino; Rt0 is hydrogen, halo, (Cl-C6)alkyl; Ru and R12 are independently hydrogen, (Cl-C6)alkyl, (Cl-C6)alkoxy, arylalkyl, (C3-C8)cycloalkyl, (C3- C8)cycloalkylmethyl, 4-(N-methylpipcridinyi), pyndyl, or Rn and R,o can be taken together to form a 4,5,6, or 7 mernbered ring, or Rn and R12 can be taken together to form a 3,4, 5,6, or 7 membered ring; Ru is hydrogen, (Cl-C6)alkyl, 2-melhoxyphenyl, 2-pyridimidinyl; Ru is 2-pyrimidinyl, N-methyl-2-imidazolyt, 4-chlorophenyl, 2- pyridylmethyl; R,$ is (Cl-C6)alkyl, N-methyl-4-imidazolyl; R|6 is hydrogen, halo, arylalkyl, aryl, wherein: Q2 is hydrogen, 4-imidai:o)yl, or C(O)NR24R25 when o and p are independently 0-2; Q2 is OR23, NR24R25, or N-roorpholino, when o and p are independently 0-2, but one or the other of o or p is not 0; Rjo is hydrogen, or (C1 -C6)alkyl; R2| is hydrogen, (Cl - C6)alkyl, or R2| and R2o can be taken together 10 form a 4, 5,6, or 7 membered ring; R22 is hydrogen, (Cl-C6)alkyl, arylalkyl, aryl, or RJI and R22 can be taken together to be a 3, 4, 5,6, 7 membered ring; R23 is hydrogen or (CJ-C6)alkyl; R24 is hydrogen, (Cl- C6)alkyl, or R2A and R2$ can be taken together to form a 3, 4, 5, 6, or 7 membered ring, or R24 and Rj0 can be taken together to form a 6 or 7 membered ring; R» is hydrogen, (C1 - C6)alkyl, or acetyl, wherein: R32 and R33 are each independently hydrogen, (Cl-C6)alkyl, acetyl, (Cl- C4)alkylsulphonyl, or R32 and R33 can be taken together to form a 4, 5, 6, or 7 membercd ring, or a group of the formula wherein: X2 is CH2, O, or N; q is 2-3 except when Qj is a bond, q is 0-3; Q3 is NR3«,R37l or OR.™, and RM is hydrogen, or Rj? and Q3 can be taken together to form a 5 membercd ring; R36, R37, and R3» are each independently hydrogen, or (Cl-C6)aJkyl, or a group of the formula wherein: X3 \$ cyano, carboxamide, N,N-dimethylcarboxamide, N,N- dimethylthiocarboxamide, N.N-dimethylaminomethyl, 4-methylpiperazin-lyl-methyl or carboxylate, wherein: Q6 is NR^R*,; r is 2-3; F4o is hydrogen, or (Cl- hydrogen, (Cl-C6)alkyl, or R*, and R40 can be taken together to form a 6 or 7 membered ring, wherein: Ch is hydroxy, methoxy, dimethylamino, or N-piperidiny); with the proviso that when one of Rl or R2 is unsubtituted or substituted phenyl, then the other cannot be unsubstituted or substituted phenyl or thiophen-2-yl; and with the proviso that when R2 is quinolin-4-yl, substitution at the quinoline 7-position cannot include an aryl, heieroaryl, fused aryl, or fused heteroaryl; k is 1-8; R3 is one or more of the following: hydrogen; (Cl-C4>lkyl; (Cl- C4)aJkylhydroxy;hydroxy;N,N-di(Cl-C4)alkylamino(C1-C4)alkoxv;benryloxvmethyl; phenyloxymethyl; oxo; carboxyi; [C\-C4) alkylaryl; benzyloxy; acetaxy; amino(CI- C4)alkyl; (C2-C4>lkenyl; halo; -O-(C1-C4)alkyl; chlorophenethyl; acetonitrile; unsubsituted or substituted phenyl; wherein the substitution may be one or more of the following: (Cl -C6)alkoxy, halo, carboxy, or (C1 -C6)alkoxycarbonyl; and the pharmaceutically acceptable salts esters and prodrugs thereof. is a five or six membered saturated ring; R1 is defined as in Claim I; R21 is hydrogen; (C1-C6)dkyl; (Cl-C6)alkylthio; (Cl-C6)alkoxy; halo; thiophenyl; aminophenyl; N-pynolidino; N-morpholino; R6' and R7' are independently one or more of the following: hydrogen, (Cl- C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (CI-C6) alkylhalide, (Cl-C6)alkoxy, (C2- C6)alkenyloxy, (C2-C6)alkynykiKy»(Cl-C6)alkylthio, (Cl-C6)alkylsulphinyl, (Cl- C6)alkylsulphonyt, (C)-C6)alkyi«nino, di-[(Cl-C6)alkyl]amino, (Cl - C6)alkoxycarbonyl, N-(C1 -C6>*ylcarbamoyJ, N,N-di-[(C1 -C6)alkyl]carbamoyl, aminooxy, N-(C1-C6)alkyl ammooxy, N,N-di-[(Cl-C6)alkyl]aminooxy, (C2- C6)alkanoyt, (C2-C6)alkanoyl C6)alkanoy1amino, (C3-C6)alkeMoylamino, N-(C1-C6)alkyl-(C3-C6)alkenoylamino, (C3- C6)alkvnoylamino, N-(C1-C6)alkyl-(C3-C6)alkynoylamino, sulphamoyl, N-(CI- C6>lkylsulphamoyl, N,N-di-[(Cl-C6)a!ky)]su]priamoyl, (Cl -C6)alkanesulphonylamim N-(C1-C6)alkyl-(CI-C6)alkanesulphonylamino, carboxamidc, ethylene, phcnyl, ihiophcnyl, aminophenyl, phenylthio, halo, cyano, pyridinyl, arylalkyl, hydroxy, N- pynrolidino, N-morpholino, carboxyl, [5-phenyl-l,2,4-oxadiazolc-3-yl]methoxy, 6- methyl-pyridazin-3-yloxy, (5-oxo-:i-pyrrolidinyl)methoxy, 2-(4,5-dihydro-l H- imidazolyl), N, N-dialkykarbamoyloxy, 1 -hydroxy- l-mcihylethyl, 4-fluorophenyi, 3,4- methylenedioxyphenyt, trifluoromcthyl, trifluoromethoxy, or a group of the formula wherein: X| is O, N, S, SO^NRu, 0(0), or bond; Qi is hydrogen, phenyl, 5-(2,2- dif1uoro-l,3-benzodioxolyl), C(OX!s, or pyridyl when m and n are independently 0-2, except when one is 0 the other cannot be 0; Qi is ORn, NRnR,j, halo, N-morpholino, N-pipera2ino-N'Ru, N-imidazolyl, N-pyrazolyl, N-triazolyl, N-(4-piperidinylpiperidine), SO^Ru, SOR|4, NHSO]R|}, acetamido, N-phthalimido, N-oxazolidino, N-imidazolino, N- benzoxazolidino, N-pyrolidinonyl, N(N'-methylbenzimidazolino), N,N-di(Cl- C4)alkylamino(CI-C4)alkoxy, N-benzimidazolino; when m and n are independently 0-2, but one or the other of m or n is not 0; Qi is hydroxy, methoxy, amino, diethylamino, dimethylamino; Rio is hydrogen, halo, (Cl-C6)alkyl; Ru and R12 are independently hydrogen, (Cl-C6>lkyl, (Cl-C6)alkoxy, arylalkyl, cycloalkyl, cycloalkylmethyl, 4-(N- methylpiperidinyl), pyridyl, or Ru and Rio can be taken together to form a 4, 5,6, or 7 membered ring, or Ru and Ru can be taken together to form a 3,4, 5,6, or 7 membered ring; Ru is hydrogen, (Cl-C6)alkyl 1, 2-methoxyphenyl; Rl4 is 2-pyrimidtnyl, N-mcthyl-2- imidazolyl, 4-chlorophenyl, 2-pyriclylmethyl; RtJ is (Cl-C6)alkyl, N-methyl-4- imidazolyl; Rl6 is hydrogen, halo, *rylalkyl, aryl, wherein: Q2 is hydrogen, 4-imidazoJyl, or C(O)NR24R25 when o and p are independently 0-2; Q2 is ORj3, NR24R25, or N-moipholino, when o and p are independently 0-2, but one or the other of o or p is not 0; R20 i«i hydrogen, or (Cl -C6)alkyl; Rj( is hydrogen, (CI- C6)a!kyl, or R2) and R20 can be taken together to form a 4, 5,6, or 7 membered ring; R22 is hydrogen, (Cl«C6)alkyl, arylalkyl, aryl, or R21 and R22 can be taken together to be a 3, 4, 5,6, 7 membered ring; R2J is hydrogen or (Cl-C6)alkyl; R*» is hydrogen, (Cl- C6)alkyl, or R24 and R2S can be taken together to form a 3,4,5,6, or 7 membered ring, or RM and R» can be taken together to form a 6 or 7 membered ring; R2$ is hydrogen, (Cl- C6)alky], or acetyl, wherein: Rw and R33 are each independently hydrogen, (Cl-C6)alkyl, acetyl, alkylsulphonyl, or R32 and R33 can be token together to form a 4,5,6, or 7 membered ring, wherein: X2 is CH2,0, or N; q is 2-3 except when Qj is a bond, q is 0-3; Q3 is NR^^, OR3», or a bond; R3S is hydrogen, or R3J and Q3 (when Q3 is a bond) can be taken together to form a 5 membered ring; Rw, R3?, and RM are each independently hydrogen, or (Cl-C6)alkyl, or a group of the formula wherein: X3 is cyano, carboxamide, N,N-dimeihylcarboxamide, N,N- dimethylthiocarboxamide, N,N-dimcthylaminomethyl, 4-mcthylpiperazin-lyl-methyl or carboxylate, wherein: Q6 is NR«,R«; r is 2-3; R* is hydrogen, or (Cl-C6)alkyl; R41 and R42are hydrogen, (Cl-C6)alkyl, or R41 and R40 can be taken together to form a 6 or 7 membered ring, wherein: Q7 is hydroxy, methoxy, or N-piperidinyl; k is I -8; R3 is one or mott of the following: hydrogen; (C1-C4) alkyl; (C1-C4) alkylhydroxy; hydroxy; N,N-di(Cl-C4)alkylamino(Cl-C4)alkoxy; benzyl oxymcthyl; phcnyloxymethyl; oxo; carboxyl;(Cl-C4) alkylaryl; benzyloxy; acetoxy; amino(Cl- C4)alkyl; (C2-C4) alkenyl; halo; -0-(CI-C4) alkyl; chiorophenethyl; acetonitrile; phenyl; or an optionally substituted phenyl; wherein the substitution may be one or more of the following: (CI -C6)alkoxy, halo, carboxy, or (C1 -C6)alkoxycarbonyl; with the proviso that R7' cannot be aryl; heteroaryl; fused aryl; or fused heteroaryl. and the pharmaceutically acceptable salts, esters and prodrugs thereof. is a five or six membered ring; R6 may be one or more of the following: hydrogen, (Cl-C6)alkyl, (C2- C6)alkenyl, (C2-C6)alkynyl, (Cl-C6)*lkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy> (C1 •C6)a!kylthio, (C1 -C6)alkylsulphii iyl, (C1 -C6)alkylsulphonyl, (C1 -C6)alkylamino, di-[(Cl-C6)alkyl]amino, (Cl-C6>lko>;ycarbonyl, N-(C1-C6>lkylcarbamoyl, N,N-di- [(CI-C6)alkyl]carbamoyl, (C2-C6)alkanoyJ, (C2-C6)alkanoyk>xy, (C2- C6)alkanoylamino, N-(C1-C6)alkyl-(C2-C6)alkanoylamino, (C3-C6)alkenoy)amino, N- (Cl -C6)alkyl-(C3-C6)alkenoylammo, :C3-C6)alkynoylamino, N-(C1 -C6)alkyl-(C3- C6)alkynoylamino, N-(C1-C6)alkylsulphamoyl, N,N-di-[(Cl-C6)alkyl]sulphamoyl, (Cl- C6]alkanesulphonylamino, N-(C1-C6)ulkyl-(C]-C6)alkanesulphonylamino, carboxamide, ethylene, thiophenyl, aminophenyt tri fluoromethyl, halo, trifluoromethoxy, hydroxymclhyl, N-pyrrolidino, N-morftholino, phenylthio, dialkylaminomcthyl, methoxyphenyl, amino, hydroxy, carboxyl, phenyl, arylalky, R2" is unsubstituted or substituted quinoline-8-yl; unsubstinited or substituted quinoline-6-yl; unsubsiituted or substituted 1-naphthyl; unsubstituted or substituted 2- naphthy); unsubsiituted or substituted 3,4-methylenedioxyphenyl; unsbustituted or substituted 3,4-cthylcncdioxyphenyl; unsubstituted or substituted benzolhiophen-2-yl; wherein the substitution may independently be one or more of the following: (CI - C6)alkyl, (C2-C6)alkenyl, (C2-C6)»lkynyl, (CI-C6) alkylhalide, (Cl-C6)alkoxy, (C2- C6)alkenyloxy, (C2-C6)alkyny!oxy, (CI-C6)aJkylthio, (C1-C6)alkylsulphinyl, (Cl- C6)alkylsulphonyl, (Cl-C6)alkylaiwno, di-{(Cl-C6)alkyl]amino, (Cl- C6)alkoxycarbonyl, N-(C1 -C6)alkylcarbamoyl, N,N-di-[(Cl -C6)alkyl]carbamoyl, aminooxy, N-(C1 -C6)alkyl aminooay, N,N-di-((CI -C6)alkyl)amindoxy, (C2- C6)alkanoyl, (C2-C6)a]kanoy]oxy, iC2-C6)alkanoyJamino, N-(CI-C6)alkyl-(C2- C6)a1kanoylamino, (C3-C6)alkenoylamino, N~(Cl-C6)alkyl-(C3-C6)alkenoylamino, (C3- C6)alkynoylamino, N-(C1-C6)alkyl-(C3-C6)alkynoylaniino, sulphamoyl, N-(C1- C6)a!kylsulphamoyl, N,N-di-[(Cl-C6)alkyl]sulphamoyl, (Cl-C6)alkanesulphonylamino, N- pyrrolidino, N-morpholino, carboxyl, [5-phenyl-l,2,4-oxadiazole-3-yl]methoxy, 6- methyl-pyrida2in-3-yloxy, (5-oxo-2 -pyrrolidinyl)methoxy, 2-(4,5-dihydro-l H- imidazolyl), N, N-dialkylcarbamoyloxy, 1 -hydroxy-1-methylethyl, 4-fluorophenyl, 3,4- methylenedioxyphenyl, trifluoromethyl, trifluoromethoxy, or a group of the formula wherein: Xf is O, N, S, SO2.NRn, C(O), or bond; Qi is hydrogen, phenyl, 5-(2,2- difluoro-l,3-benzodioxolyl), C(O)Q.i, or pyridyl when m and n are independently 0-2, except when one is 0 the other cannot be 0; Qi is ORM, NR,,R|2, halo, N-morpholino, N-piperazino-N'Ri3, N-imidazolyl, N-pyra2olyl, N-triazolyl, N-(4-piperidinylpipcridine), SO3R14, SORM, NHSOJRIJ, acetamido, N-phtbalimido, N-oxa2olidino, N-imidazolino, N- benzoxazolidino, N-pyrolidinonyl, N(N*-methylbenzimidazolino), N,N-di(CI- C4)alkylamino(Cl-C4)alkoxy, N-benzimidazolino; when m and n are independently 0-2, but one or the other of m or n is not 0; Qs is hydroxy, methoxy, amino, diethylamino, dimethylamino; R,o is hydrogen, halo, (Cl-C6)alkyl; Ru and R,2 are independently hydrogen, (Cl-C6)alkyl, (C1-C6>alkoxy, arylalkyl, cycloalkyl, cycloalkylmethyl, 4-(N- methylpiperidinyl), pyridyl, or Ru and R10 can be taken together to form a 4,5,6, or 7 membered ring, or R, \ and Ru am be taken together to form a 3,4, 5,6, or 7 membered ring; Ru is hydrogen, (Cl-C6)alkyl, 2-methoxyphenyl; R)4 is 2-pyrimidinyl, N-mcthyl-2- imidazolyl, 4-chlorophenyl; 2-pyridylmethyl; R15 is (Cl-C6)alkyl, N-methyl-4- imidazolyl; R!6 is hydrogen, halo, arylalkyl, aryl, wherein: Qi is hydrogen, 4-imidazolyl, or C(O)NRj4Rj5 when o and p arc independently 0-2; Q3 is OR2J, NR24R2S, or N-niorpholino, when o and p arc independently 0-2, but one or the other of o or p is not 0; R^ is hydrogen, or (Cl-C6)alkyl; R2) is hydrogen, (C1- C6)alkyl, or R2i and R30 can be taken together to form a 4, S, 6, or 7 membered ring; R22 is hydrogen, (Cl-C6)alkyl, arylaikyl, aryl, or R21 and R22 can be taken together to be a 3, 4,5,6,7 membered ring; R2? is hydrogen or (CI -C6)alkyl; R24 is hydrogen, (C1 - C6)alkyl, or R24 and R2j can be taken together to form a 3,4, 5,6, or 7 membered ring, or R24 and R20 can be taken together to form a 6 or 7 membered ring; R2J is hydrogen, (Cl- C6)alkyi, or acetyl, 5. A compound as claimed in claim 1, wherein the compound is selected from the group comprising: a) 6-Bromo-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3-yl)- quinoline, b) 3-Pyridin-4-yl-2-pyridin-2-yl-5,6-djhydro-4H-pyiTOlo[ 1,2-b]pyrazole, c) 2-(6-Mcthyl-pyridin-2«yl)-3-p-tolyl-5,6-dihydro-4H-pyrrolo[I,2- bjpyrazole, d) 4-[3-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pym>lo[ 1 ,2-b]pyrazol-2-yl]- quinolinc, e) 2-(6-Methy!-pyr»din-2-yl>3-naphthalen-l-yI-5,6-dihydro-4H-pyrTolo[l,2- b]pyrazolc, f) 2-(6-Mcthy]-pyndin-2-yl)-3-pyridin-3-yl-5t6-dihydro-4H-pyrTolo[ 1,2- b]pyrazole, g) 3-(4-FIuoro-naplithalcn-1 -yl)-2-(6-methyl-pyridm-2-yl)-5,6-dihydro-4H- pyrTolo[ 1,2-b3pyrazole, h) 3-(3,4-Difluoro-phenyl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazolc, i) 1 -(2- cth yl ideneaminoj-pyrrol id in-2n)ne, j) 7-Meihoxy-4- quinolinc, k) 7-Bcn2yloxy-6-rncthoxy-4- b]pyra2ol-3-yl)-quinoline, I) 6-(2-Pyridin-2-y m) 6-(2-(6-Mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazo1-3-yl]- quinolinc, n) 3-Naphthalen-2-yJ-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ I ^-b]pyrazolc, o) 2-(6-Mcthyl-pyridin-2-yl)-3-naphthalcn-2-yl-5,6-dihydro-4H-pym)lo[ 1,2- b]pyrazolc, p) 3-(4-Fluoro-phenyl)-2-(6-trif1uoromcthyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo( 1,2-b]pyrazole, q) 4-(Quinolin-4-yl)-3-(5-fluoropyridin-2-yl)-5,6-dihydro-4H-pynrolo(l,2- b]pyrazolc, r) 4-(7-BromoquinoIin-4-yl>3-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l,2- bjpyrazole, s) (Quinolin-4-yl>3-(2,4-diJ7uorophcnyl}-5,6-dihydro-4H-pyrrolo{l,2- bjpyrazole, 0 4-(2-Pyrazin-2-yl-5,6-dihydro-4H-pyTTolo[ 1,2-b]pyrazol-3-yl>quinoline, u) 4-(5-Mcthyl-2-oyridin-2-yI-5,6-dihydro-4H-pym>lo[l ,2-b]pyrazol-3-y])- quinoline, v) 6-BroTno-4-[2-|6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pym)Ioll^- b]pyrazol-3-yl]-quinolinc, w) 4-[2-(6-Methyl pyridin-2-yl)-5,6-dihydro-4H-pyrr6lo[ 1,2-bJpyrazol-3-yl]- 6-trifluoromcthyJ-quinoline, x) 3-(3-Chloro-4-lluoro-phenyl)-2-(6-mcthyl-pyridin-2-yl>-5,6-dihydro-4H- pyrrolo[ 1,2-bjpyrazolc, y) 3-(2-Chloro-4-/luoro-phenyl)-2-(6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-bjpyrazolc, z) 3-(4-Fluoro-3-tiifluoromethyl-phcnyJ)-2-(6-mcthyl-pyridin-2-yl)-5,6- dihydro-4H-pyrrolo(! ,2-bjpyrazolc, aa) 2-(6-Mcthyl-pyiidin-2-yl)-3-(2,4,5-trifluoro-phenyI)-5,6- bb) 8-FluOTO-4-[2-(('-mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pym>lo{ 1,2- b]pyrazol-3-y)]-quinolinc, cc) 7-Bromo-4-[2-(loI! ,2- b]pyrazol-3-yJ]-quinolinc, dd) 4-[2-(6-Methy!-pyridin-2-yl)-5,6-dihydro-4H-pyfTolo{ 1,2-b]pyrazol-3-yl]- 6-lrifluoromethoxy-quinolinc, ce) 4-(2-(6-MeJhy!-(»yridin-2-yl)-5,6-dihydro-4H-pyrrolo{ 1,2-b)pyTazol-3-yI]- 7-trifluoromethyl-quinoline, 0) 7-Mcthoxy-4-[2(6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyrTolo[l,2- b]pyrazol-3-yl]-quinolinc. gg) 3-(2-Chloro-pyrid«n-4-yl)-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b)pyrazole, hh) [2-(6-MethyJ-pyridin-2-yl)-3- «0 [3-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrTO lo[ 1,2-b]pyrazol-6-yl]-methanol, jj) 4-[2-(tf-Chloro-pyridin-2-yl>-5-(4-fluorophenyl)-5,6-dihydro-4H- pyrro lo[ 1,2-b]pyrazol-3-yl]-quit»oHnc, kk) 4-[2-(6-Ethoxy-pyridin-2-yl)-5-(4-fluoro-phenyl>5,6-dihydro-4H- pyrrolo[J,2-b]pyrazol-3-yl]-qumoline, 11) (S)-4-[6-Bcnzyloxymcthyl-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl]-7-chloro-quinolinc, ' mm) (S)-4-[6-BenzyIa«ymcthyl-2-(6-chloro-pyridin-2-yl)-5,6-djhydro-4H- pyrro] o[ 1,2-b]pyrazol-3-yl)-quii«)Hnc, nn) 4-{2-(6-Mcthyl-pyridin-2-yl)-3-quinolin-4-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-5-yl].bcnzoic acid ethyl ester, oo) 3-(4-Fluoro-phenyI)-5,5-dimclhyl-2-(6-inethyl-pyridin-2-yl)-5,6-dihydro- 4H-pyn-olo[ 1,2-b)pyrazole, pp) (R)-6-Benzyloxyinethyl-3-(4-fluoro-pbenyl>2-(6-inethyl-pyridin-2-yl)- 5,6-dihydro-4H-pyrTolo[ 1,2-b]pyrazole, qq) 5-(4-Chloro-phenyl)-3-(4-fluoro-phenyl)-2-(6-methyl-pyridin-2-yl)-5,6- dihydro-4H-pynolo[ 1,2-b]pyrasx>le, rr) 4-[2-(3-Trifluorc4nethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[ 1,5- ajpyrid in*3-yl]-quinoline, ss) 4-[2-(4-Trifluore«nethyl-phenyl)-4.5,6,7-tctrahydro-pyrazolo( 1,5- ajpyrid in-3-yI]-quinolinc, tt) 4-[2-{4-Chloro-iihenyl)-4,5,6,7-tetrahydro-pyrazolo[ 1,5-a3pyridin-3-yl)- quinoline, ou) 4-[2-(3-Chloro-j)hcmyl>4,5,6,7-ielrahydro-pyrazo)o( 1,5-alpyridin-3-y)- quinoline, w) 4-[2- b)pyrazol-3- y]]-quinol ine, ww) 4-{2-(3-Fluoro-! -irifluoromethyJ-phenyl)-4,5,6,7-tetrahydro-pyrazolo[ 1,5- a]pyridin-3-yl]-quinoline, xx) 4-(2-Phenyl-4,5,6,7-tctrahydro-pyrazo1o[ 1,5-a)pyridin-3-yl)-quinoline, yy) 4-(2-Pyridin-2-yl-4,5,6,7-teirahydro-pyrazolo[ 1,5-alpyridin-3-yl)- (l,10]phenanthroline, 22) 4-[2-(4-FIuoro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[ 1,5-a]pyridin-3-yl]- quinolinc, aaa) 4-[2-(3-Tri fluon imcthoxy-phenyl)-4,5,6,7-tetrahydro-pyra2olo[ 1,5- a]pyridJn-3-yl]-quinolinc, bbb) 4-[2-(2-Fluoro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[ 1,5-a]pyridin-3-yl]- quinolinc, ccc) 4-(2-QuinoIin-2- yl-4,5,6,7-tctrahydro-pyra2olo[ 1,5-a]pyridin-3-yl)- quinolinc, ddd) 4-[2-(4-Ethyl-pyridin-2-yI)~4,5,6,7-tetrahydio-pyrazolo( 1,5-a]pyridin-3- yl]-quinolinc, ccc) 4-(2-Quinolin-2- yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, ffT) 2-(3-Quinolin-4- yl-4,5,6,7-tetrahydro-pyra2olo[ 1,5-a]pyridin-2-yl)- [l,8]naphthyridine, ggg) 4-(5-(4-Fluoro-phcnyl)-2-p:yridin-2-yl-5,6-dihydro-4H-pym)lo[l,2- b]pyrazol-3-yJ]-quino!inc, hhh) 4-(6-Hydroxymcthyl-2-pyridin-2-yl-5,6-dihydro-4H-pynolo[Ir2- b]pyrazol-3yl)-quinolinc, in) 4-(3-Pyridin-2-y-5,6-dihydro-4H-pytTolo[l,2-b]pyrazol-2-yl)-quiiK>line, jjj) 4-(4-Melhyl-2-pwidin-2-yl-5,6-dihydro-4H-pyrrolo[l^-b]pyrazoI-3-yl)- quinoline, kkk) 4-(5-Bcnzyl-2-p:Tidin-2-yl-5,6-dihydro-4H-pyrrolo[ J ^-b]pyrazol-3-yl)- quinoline, 111) 4-(5-Phenethyl-2-pyridin-2- yl-3,6-dihydro-4H-pyrTolo[l ^-b]pyrazol-3- yl)-quinolinc, mmm) 4-(5-Phcnyl-2-p)Tidin-2-yl-5,6-dihydro-4HpyrTob[l,2-b]pyrazol-3-yl)- quinolinc, nnn) 4-{2-(3-Trifluorom»:ihylphcnyt)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl]-quinoline, ooo) 4-[2-(4-Trifluoromtthyl-phenyl>5,6-dihydro-4H-pym>lo[ 1,2-bJpyrazol-3- yl]-quinoline, PPP) 4-(2-Phcnyl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, qqq) 2-Chloro-4-(2-pyrHlin-2-yl-5,6-dihydro-4H-pyrroIo[ 1,2-b]pyrazol-3-yl)- quinoline, . mr) 6,8-Dimethoxy-4-(7-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo(l,2b]pyra2ol-3-yI]-quinolwe, sss) 4-[2-(6-Bromo-pyridin-2-yl)-5,6-dihydro-4H«pyrrolo(l ,2-b]pyr«zol-3-yl]- quinoline, ttt) 6,8-DimcJhoxy-4-(;-pyridin-2 -yl-5,6-dihydro-4H-pyrn>k)[ 1,2b]pyrazol-3- yl]-quinoline, uuu) 3-(4-FluorophcnyJ>2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b}pyrazole, wv) 3-(4-Meihoxy-phcnyl)-2-pyridin-2-yl-5,6-dihydro-4H-pyrTolo[l,2- b]pyrazole, www) 3-(4-Fluorophcnyl> 2-(6-methy)pyridin-2-yl)-5,6-dihydro-4H-pyrTolo[ \ ,2- bjpyrazole, xxx) 3-2-(6-mcthylpyridin-2-yl)-5.6-dihydro-4H- pyrroJo[ 1,2-b)pyrazole, yyy) 4- zzz) 4-{2-(6-Propylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo{l,2-b]pyra2ol-3-yl]- quinofine, aaaa) 4-[2-(6-lsopropylpyridin-2-yl)-5,6-dihydro-4H-pyTTolo{ 1,2-b]pyrazol-3- yljquinolinc, bbbb) 4-[2-(6-E«hy)-pyridia.2-yl)-5,6-dihydro-4H-pyrn>lot 1,2-b)pyrazol-3- yl]quinoline, cccc) 4-{2-(6-Mcthyl-pyhdio-2-yl)-5,6-dihydro-4H-pyiTolo[l,2-b]pyra2ol-3-yl]- quinoline, dddd) 4-[2-(3-Fluorophcnyl>-5,6-dihydro-4H-pyiTolo[ 1,2-b)pyrazol-3-yl]- quinoline, eccc) 4-[2-(2-Fluoro-phenyl)-5,6~dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]- quinoline, ffil) 4-[2-(4-Fluoro-phenyI)-5,6-dihydro-4H-pyrrolo[l,2-b)pyrazol-3-yl]- quinolinc, gggg) 4-(2-{3-Trifluoromcthoxy-phcnyl)-5,6-dihydrt>-4H-pym>lol 1,2-b]pyrazol- 3-yl]-quinoline, hhhh) 4-(2i(4-Chloro-p:yridin-2-yl>5,6-dihydro-4H-pyrrolol 1,2-b)pyittol-3-yl]- quinolinc, iiii) 4-[2-(4-Fluoro-3- trifluoromclhyl-phcnyl)-5,6-dihydro-4H-pyrrolo(l ,2- bJpyrazol-3-yl]quinoline, iiii) 4.[2-(2-nuoro-3-trifluoromethyl-phenyl)-5,6-dihydro-4H-pyrrolo[I^-b]- pyrazol-3-yl]-quinolinc, ;' kkkk) 4-[5-(3-Mcthoxyphcnyl>-2-pyridin-2-yl-5,6'dihydro-4H-pyrroIo[l^- b}pyra2ol-3-yl]-quinoline, U1I) 4-{2-(4-Fluoro-3-irinuoromcthyl-phcnyl)-5-(3-methoxy-phcnyl)-5,6- dihydn -4H-pyrrolo[l,2-bJpyrazol-3-yl]-ijuinoline, mmmm) 4-(7-Chlo'o-quinolin-4-yl)-3-(6-methylpyridin-2-yl)-5,6 nnnn) 4-(7-EthoxyquinclJn-4-yl)-3-(6-mcthylpyridin-2-y))-5,6- oooo) 6-(3-Quinolin-4-> l-5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazol-2-yl)-pyridine- 2-carboxylic acid hydrochloride, pppp) 6,7-Difluoro-4-[2 (6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo(l,2- b]pyra2ol-3-yl]-quinoline, qqqq) 6,7-Dimcthoxy-4- (2-(6-mclhyl-pyridin-2-yI)-5,6-dihydio-4H-pynolo( 1,2- b}pyrazoJ-3-yl}-quinoline, nnrr) 3-Benzo[ 1,3]dioxol-5-yl-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyra2Olc, ssss) 6-(4-Fluoro-phenyl)-4-[2-(6-mcihyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyra2ol-3-yl]-quiiK)line, tttt) 6-Benzo[ 1,3]dioxol-5-yl-4-[2-(6-methyl-pyridin-2-yJ)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyra2Ol-3-yI]-quin«3line, uuuu) 4-{2-(6-Methyl-[iyridin-2-yl)-5,6-dihydro-4H-pyrTolo[ 1,2-b]pyrazol-3-yl]- 6-thiophen-2-yl-quinoline, vwv) 4-[2-(6-McthyU(»yridin-2-yl)-5,6-dihydro-4H-pyrrololl,2-b]pyrazoI-3-yl]- 6-phenyI-quinol inc. wwww) 8-(2-(6-niethyl-pyridin-2-y1)-5,6-dihydro-4H-pym>J b]pyra2ol-3-y!]-quinoline, xxxx) 3-Benzo(b]«hiophcn-2-yl-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazole, yyyy) 4-{2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo{ 1,2-b]pyrazol-3-yl)-quinoline-6- carboxyltc acid methyl ester, 7777) 4-[2-(6-Meihyl-f>yridin-2-yi)-5,6-dihydro-4H-pyrrolo[ 1 ,2-b]pyra2ol-3-yl]- quinoline-6-carboxylic acid methyl ester, aaaaa) 4-[2-(6-Meihyl-pyridin-2-y|)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl]- quinoline-7-carboxylic acid methyl ester, bbbbb) 4-[2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3-y(]-quinoline-7- carboxylic acid methyl ester, ccccc) 2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo[5,l-c]morpholine, ddddd)2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo[5,l-cJmorpholin-4-one, eeeee) Dimethyl- {3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyra2Ol-3- yl)-quinolin-7-yloxy]-propyl}-8»minc, ffTTf) {3-(6-Methoxy-4-(2-pyridiir>.2-yl-5,6-dihydro-4H-pyrTolo{l ^-b]pyra2ol-3- yl)-quinoIin-7-yloxy]-propyl}- pyrrolof 1,2-b]pyrazol-3-yl)-quinolin-7-yloxy]-propyl}-amine, hhhhh) Dicthyl- {3-[4- quinolin-7-yIoxy]-propyl} -amine, iiiii) Ethyl-methyl-{3-{4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrok>fl,2-b]pyrazol- 3-yl)-quinolin-7-yloxy]-propyl -amine, iiiij) 3-[4-(2-Pyridin- 2-yl-5,6-dihydro-4H-pyrrolol 1,2-b]pyrazol-3-yl)-quinolin- 7-yloxy]-propylamine, kkkkk) 7-[3-(4-Methyl-j)iperazin-1 -yl)-propoxy]-4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[ 1,2-b3pyrazol-3-yl)-quinoline, Hill) Benzyl-meihyl-,3-l4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolollt2- b]pyrazo!-3-yl)-quinolin-7-yIo>,yJ-propyl}-aminc, mmmmm) 7-(3-P iperidin-1 -yl.propoxy)-4-(2-pyridin-2-yI-5,6-dihydro-4H- pynrolo[ 1,2-b]pyrazol-3-yl)-qu.noltne, nnnnn) 4-(2-Pyridin-2-yi-5,6-dihydro-4H-pyrrolo[l ,2-b]pyra2ol-3-yl)-7-(3- pyrrolidin-l-yl-propoxy)-quino1ine, ooooo) 7-(3-A^epan-1 -yl-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pynolo[l ,2- b]pyrazol-3-yl)-quinoline, ppppp) 7-(3-Imidazol-l -yl-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-q\iinoline, qqqqq) 7-(3-Pyf azol-1 - yl-propoxy )-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quinoline, rmrr) I1- {3-[4-(2-Pyridin-2.y|.5,,6-dihydro-4H-pyrTolol 1,2-b]pyrazol-3-yl> quinolin-7-yloxy]-propyl} -[ 1, 4*]bipiperidinyl, sssss) Cyclopropyl-(1 -methyl-piperidin-4-yl)-{3-[4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[l^-b]pyrazo!-3-y;)-quinolin-7-yloxy]-propyl}-aminc, Uttt) 4-(2-Pyridin-2- yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-7-(3- [ 1,2,3]triazol-1 -yl-propoxy)-quinoline, uuuuu) Dimcthyl-(3- {4-(2- b]pyrazol-3-y1]-quinolin-7-yloxy}-propyl)-aminc, vww) Diethyl-(3- {4- [2- bjpyrazol- 3-yl]-quinolin-7 -yloxy) -propyl)-am i ne, wwwww) CyclopropylmcthyK3- {4-(2-(6-mcthyl-pyridin-2-yl)-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-3-> 1]- xxxxx)Eihyl-mcthyl-(3-{4-[2-(6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H- pyirolof 1,2-b]pyrazol-3-yl]-cuinolin-7-yloxy}-propy!)-aminc, yyyyy) DimcthylH2-|4-(2-pyridin-2-yl-5,6-dihydro-4H-pyTTolo[1,2-b]pyrazol-3- yl)-quinolin-7-yloxy]-cthyl}-amh»e, zzzzz) Dicthyl- {2-[4 (2-pyridin- 2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yI)- quinolin-7-yloxy]-ethyl}-aminc, aaaaaa)7-{2-Piperidir -1 -y*-«thoxy)-4^2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl)-quinoline, bbbbbb) Ethy)-m«hyl-{2.[4-(2-pyridin-2-yJ-5,6-dihydro^H-pyiTo]otl,2- b]pyrazol-3-yl)-quinolin-7-yloxy)elhy)}-amine, cccccc)4-(2-Pyridin-2-yl-:5,6-dihydro-4H-pyrrolo[1,2-b)pyra2ol-3«y})-7-(2- pyrrolidin-1 -y1-ethoxy>quinolim, dddddd) 7-[2-(4-Methyl-piperazin-1 -yl)-ethoxy]-4-(2-pyridin-2-yl-5,6- dihydro«4H-pyrTOlo[ 1,2-b]pyrazctl-3-yl)-quinoline, ecceee)Dimetkyl- {3-[ 1 -OKy-4-(2-pyridin-2-yl-5,6-dihydro-4H-pynolo( 1,2- b)pyrazol-3-yl)-quinolin-7-ylox}]-propyl}-amine, ffflff) 7-M«thylsulfanyi-4-(2-pyridin-2-yl-5,6-dihydro-4H-pytTolo(1,2-b]pyrazol- 3-yl)-quinoline, gggggg) 7-Ethylsulfanyl-4-(2-pyridin-2-yl-5,6-dJhydra-4H-pyiTOlo[l,2- b]pyrazol-3-yl)-quinolinc, : hhhhhh) 6-Meihylsulfanyl-4-(2-pyridin-2-y|.5,6^iihydro-4H-pyiToJo[l ,2- b]pyrazol-3-yl)-quinolinc, iiiiii) 7-Bcnzylsulfanyl-4-(2-pyridin-2-yI-5,6-dihydro-4H-pyrrolo[l,2-b)pyrazol- 3-yl)-quinoline, Jiijjj) 3-(4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinolin- 7-ylsulfanyl]-propan-1-ol, kkkkkk) Dimcthyl-{2-[4-(2-pyridm-2-yl-5,6-dihydro-4H-pyiTOlon,2- b]pyrazol-3-yl)-quinolin-7-yJsulfcnyl]-«thyl}-aminc, IIIIII) Dimethyl [C-CS-^inolin-^yl-S^-dihydro^H-pytTolof 1,2-blpyrazol-2-yl)- pyridin-2-yl-mcthyl]aminc, mmmmmm) 7-(2-Propoxy-ethoxy)-4- pyrrolofl ,2-b]pyn»2ol-3-yl)-qninoUne, nnnnnn) N,N-Dimrthyl-N'-f4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrTolo[l ,2- b}pyrazol-3-yl)-pyridin-2-yl]-ethane-1,2-diaminc, oooooo) N,N-Din»ethyl-N'-[4- b]pyrazol-3- yl)-pyridin-2-yI]- propane* 1,3-diamine, PPPPPp) 3- {3-[«»- yl)-quinolin-7-yloxy]-propyl)-oxazolidin-2-one. qqqqqq) I - {3-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyTTolo[ 1,2-b]pyrazol-3- yl)-quinolin-7-yloxy]-propyl | -iraidazolidin-2-onc, m-nr) 3-{3-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyra2ol-3-yl)- q u i nol in-7-yloxy]-propyl}-3 H-bciJ20oxazol«2-one, ssssss) Dimethyl-{2- {4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-pyridin-2-ylsulfanyl}-ethyl-amine, utttt) 4-(2-Pyridin-2-yl-5,6-dihydro~4H pyiTolo[ 1,2-b]pyrazol-3-yl)-2pym>lidin- 1-yl-quinoline, uuuuuu) 2-PhcnylsulfanyJ-4-{2-pyridin-2-yl-5,6-dihydro-4H-pyTTolo[ 1,2- b]pyrazol-3-yl)-quinol i ne, www) 2-MorphoIin-4-yl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[lt2- b]pyrazol-3-yl)-quinoline, wwwwww) 2-Ethylsulfanyl-4-(2-pyridin-2-yl-5,6-dihydn>-4H-pyrrolo[l £• b]pyrazoI-3-yl)-quinoline, ; xxxxxx) Phcnyl-[4-(:2-pyridin-2-yl-5,6-dihydro-4H-pytTOlo{l,2-b]pyra20l-3- yl)-quinolin-2-yl]-amine, yyyyyy) 2-Methoxy-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrTOlo[ 1,2- b]pyrazol-3-yl)-quinoline, zzzzzz)2-Ethoxy-4-(2-pyridin-2-yl-5,6-dihydTO-4H-pyrrolo(l,2-b]pyrazol-3-y])- quinoline, aaaaaaa) • 4-[2-(6-Phenylsulfanyl-pyridin-2-yl)-S,6-dihydro-4H-pyrTolo[l ,2- b]pyrazo!-3-yl]-quinoline, bbbbbbb) Phcnyl-[6-{ J-quinolin-4-yl-5,6-dihydro-4H-pyiTOlo[ 1 J!-b]pyrazol- 2-yI)-pyridin-2-y]]-aminc, ccccccc) 4- {2-[6-(4-Mcthoxy-phenyl)-pyridin-2-ylJ-5,6-dihydro-4H- pyrrolo[ 1,2-bJpyrazol-3-yl }-quinolinc, ddddddd) 4-[2-(6-Pho»yl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l ,2- b]pyrazol-3-yl]-quinoline, eeeeeee) 4-[2- b]pyrazol-3-yl]-quinolinc, frfTffT) 4-(2-(6-Pyrrolidin- l-yI-pyridin-2-yl)-5,6-dihydro-4H-pyrroloI 1,2- b]pyrazol-3-yl]-quinolinc, ggggggg) 4-[2-(6-Me«hoxy-pyridin-2-yl)-5,6-dihydro-4H-pyiTolo[l ,2- b]pyrazol-3-yl]-quinolin€, hhhhhhh) 2-{3-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrTolo[l,2-b]pyrazol-3- yl)-quJnolin-7-yloxy]-propyl}-soindolc-l ,3-dionc, iiiiiii) 7-(3-Fluoro-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro«4H-pynolo[l,2- b]pyrazol-3-yl)-quinoline, Ijijiii) 7-(3-Fluoro-propoxy)-4-(2 -pyridin-2-yl-5,6-djhydro-4H-pyrrolo[ 1,2- b]pyrarol-3-yl)-quinolinc, kkkkkkk) ' 7-(3-Ch»oro-propoxy)-4-(2-pyridin-2-yl-5,6-dihydfO-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, 1IH11I) 7-(3-Chloro-propoxy>6-methoxy-4-(2-pyridin-2-yl-5,6- mmmmmmm) 7 - 4H-pyrrolo{ 1,2-b]pyrazol-3-yl]- nnnnnnn) (1 - {3-["'-(2-Chloro-elhoxy)-quinolin-4-yl]-5,6-dihydio-4H- pyiroioj 1,2-b]pyrazol-2-yl} >propenyl)-inethylenc-amine, ooooooo) N,N-Diethyl-2-[4-(2-pyridin-2-yI-5,6-dJhydro-4H-pym>Jo[ 1,2- b]pyrazo)-3-yl)-quinolin-7-yl 5,6-dihydro-4H-pyrrolo( 1,2-b |pyiazo1-3-yl)-quinoHne, qqqqqqq) DimcthyJ-{4-{4-(2-pyndin-2-yl-5,6-dihydro-4H-pyrrolo[1,2- b]pyrazoI-3-yl)-pyridin-2-ylo:{y]-butyl}-aminc, rrmrr) 1 - (3-[4- pyridin-2-yloxyJ-propyl} -pyr-olidin-2-one, sssssss) 7-( I -Metbyt-piperidin-3-ylmethoxy)-4- dihydro-4H-pyrrolo[l,2-b]pyra2ol-3-yl)-quinoHnc, tntttt) 7-(3-N ,N -Dime(hyi«minQ-2-methyl-propyloxy)-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrro!o[ 1,2-b]pyiazol-3-yl)-quinolinc, uuuuuuu) 4-[2-(6-M«lh>1-pyridin-2-yl>5,6-dihydro-4H-pyTTolot 1,2- b]pyrazol-3-yl]-7-propoxy-qninoline, vvwvvv) 4-[6-Bcnzyioxynic(hy|.2-(6-methyl-pyridin-2-yI)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl]-cuinolii>c, wwwwwww) {4-[2-i6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrTolo[l ,2- b]pyrazol-3-yl]-quinolin-7-yioxy}-acetic acid methyl ester, xxxxxxx) 7-lsopropoxy-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl]-quinoline, yyyyyyy) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrroU>[l ,2- b]pymolO-yl]-7-(3-morpholin-4-y)-propoxy)>quinoline, Z2Z2ZZZ) 4-(6-Benzyloxymcthyl-2-pyridin-2-yl-5,6-dihydro-4H-pynolo[ 1,2- b]pyra2ol-6-yl)-quinolinc, aaaaaaaa) 7-Benzylox y-2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo{ 1,5- a]pjpcridinc, bbbbbbbb) 2-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-aceiamide, cccccccc) 7-(5-Phcnyl-[ 1,2,4]oxadiazol-3-ylmcthoxy>-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinoHnc, : dddddddd) 7-(2,2-Difluoro-benzo{ 1,3]dioxol-5-ylmcthoxy)-4-(2-pyridin-2-yl- 5,6-dihydro-4H-pyrrolo[ 1,2-b]pyiazol-3-yl)-quinolinc, eceeeeee) 7-[2-((2S> I -Mcthyl-pyrrolidin-2-yl)-cthoxy]-4-(2-pyridin-2-yl- 5,6-dihydro-4H-pynrolo[ 1,2-b]pyj-azol-3-yl)-quinoline, nTffTTfY)5-[4^2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazoI-3-yI)-quinolin- 7-yloxymcthyl]-pyrrolidin-2-one) BSfiggggg) 4-(6-Phcnoxymethy!-2.-pyridin-2-yl.5,6-dihydro-4H-pyrro!o[ 1,2- b]pyrazol-3-yl).quinolinc, hhhhhhhh) 4-(6-Mcthylcne-2-pyridin-2-yl-5,6-dihVdro-4H-pyirolo[ 1,2- b]p>Tazol-3-yl)-quinolinc, iiiiiiii) 3-(4-Fluoro-phenyl)-6-mclhylene-2-(6-methyl-pyridin-2-yl)-5,6-dihydTO- 4H-pym)lo[ 1,2-b]pyrazolc, iiiiijjj) 7-(1-Mcthyl-pipendin-2-ylmelhoxy)-4-(2-pyridin-2-yl-5,6-dihydfX>-4H- pyrrolo{ I ^-b]pyrazol-3-yl>quinoline hydrochloridc, kkkkkkkk) 7-[2-(l-Mrthy!-pyiToHdin-2-y1)-cthoxy]-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[l ,2-b]pyrazcl-3-yl)-quinolinc hydrochloridc, IIIIIIII) 4-[2-(6-McthyM-wy-pyridin-2-yI)-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-yl]-quinoline 1 -oxide:, mmmmmmmm) 4-[ 2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrTolo[ 1,2- b]pyrazol-3-yl]-quinoIinc 1 -oxidt:, nnnnnnnn) 4-[2-(6-McthyJ-l-oxy-pyridin-2-yl)-5,6-dihydro-4H-pyrroJoll,2- b]pyra2ol-3-ylJ-quinolinc, oooooooo) 7-(3-Chloro-propoxy)-4-(2-pyr«'Jin-2-yl-5,6-dihydro-4H- pyrrolof) ,2-b]pyrazol-3-yl)-quinoIine 1 -oxide, PPPPPPPP) 7-Mcth»nesulfonyl-4-{2-pyTJdin-2-yl-5,6-dihydro-4H-pym)lo{l,2- b]pyrazol-3-yl)-q\iinolinc, qqqqqqqq) 3-(4-Flwwo-phenyl)-2- 4H-pyrroIot I »2-b]pyrazole, rrrrnTr)4-(Quinolin-N-1 -oxide-4-yI>3-(6-me!hylpyridin-2-yl)-3,6-dihydro-4H- pyrrolo[l,2-b] pyrazole, ssssssss) 6-Mcth4nesulfonyl-4-(2-pyridin-2-y!-5,6-dihydro-4H-pyrrolo{ 1,2- b]pyrazol-3-yl)-quinoline, ; tttttttt) 7-Ethancsulfor yl-4- 3-yl)-quinoline, uuuuuuuu) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyiTolo[) ,2-b]pyrazol-3-yl)-7-{3- (pyrimidinc-2-sulfonyl)-prop«xy)- vvwvwv) 7-{3-( I -Methyl-1 H-imida2olc-2-sulfonyl)-propoxy]-4-(2-pyridin-2- yJ-5,6-dihydro-4H-pyrrolo[ 1,2«bJpyrazoI-3-yl>quino]ine, www ww www) 7-[3-(4-Chloro-bcnzencsul fony))-propoxy]-4 »(2-pyridin-2- yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolinc, xxxxxxxx) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrroJo[ J ,2-b]pyrazoJ-3-yl)-7-[3- (pyridin- 2-yl methancsul fony )-propoxy]-quinoline, yyyyyyyy) 4-(2-P yridin-2-yl- 5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-7-[3- (pyridin-2-yJ mcthancsu I finyl )-propoxy]-quinoline, »yy»>777) 4* aaaaaaaaa) 3-{4-[2-{6-Meihyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolot 1,2- b]pyrazol-3-yl]-quinolin-7-yl}-acfylic acid methyl ester, bbbbbbbbb) 3- {4-|2-(6-MethyIpyTdin.2-yl-5,6- ccccccccc) 3- b]pyrazol-3-yl]-quinolin-6-yl}-acrylic acid methyl ester, ddddddddd) 4-[2-(6-Meihyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolol 1,2- b]pyrazol-3-yl]-7-vinyl-quinolinc, eeccceeee) 4-[2-(6-Ben2yl-pyridin-2-yl)-5,6-dihydro-4H-pyrroIo[l ,2- b)pyrazol-3-yl]-quinoline, TfTfffffT) 7-Benzyl-4-[2-(6-mcthyl-pyridin-2-yl)-5>6-dihydro-4H- pyrro1o[ 1,2-b]pyrazol-3-yl]-qukno!Jnc, ggggggggg) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-yl]-quinoline-7-cai-boxyIic acid, hhhhhhhhh) 4-[2-(6-M«hyI-pyridin-2-yl)-5,6-dihydro^H-pyrTok>{ 1,2- b]pyrazol-3-yl]-quinoline-6-caifboxyHcacid, iiiiiiiii) 3- {4-(2-(6-Mcihy!-pyridin~2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl]-quino!in-7-yl}-acrylic acid, : iiiiiijjj) 3- {4-[2-(6-Melhyl-pyridiiv-2-yl)-5,6-dihydror4H-pyiTolo{ 1,2-b]pyrazol-3- yl]-quinolin-7-yl}-propionic acid, kkkkklcJckk) 4-[2-(6-iVjethy]-pyridin-2-yl).3.quinolin-4-y!-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-5-yl]-benzoic acid, IIIIIIIII) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoHne-7- carboxylic acid cyclopentylamide, mmmmmmmmm) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl)-quinoline-7-carboxylic acid (2-morpholin-4-yl-cthyl)-annide, nnnnnnnnn) 4-(2-Py)idin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid [2-(lH-imidazol-4-yl)-cthyl]-ainide, ooooooooo) 4-(2-Pyndin-2-y]-5,6-dihydro-4H-pym>lo[ 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid (2-methylamino-ethyl)-amide, PPPPPPPPP) 4-(2-Pyiidin-2-yl-5,6-dihydro-4H-pyrrolo(l ,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid (3-methylamino-propyl)-amide, qqqqqqqqq) 4-(2-Pyddin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid (2-dimethylamino-ethyl)-amide, rnrmTr) (4-MetKyl-pipcrazin-l-yl)-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyiTolof 1,2-b]pyrazol-3-yl)-qiiinolin-7-yl]-inclhanone, sssssssss) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid cyclobuiylamide, ttuuKt)4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2.b]pyra2ol-3-yl)-quinolinc-7- carboxyiic acid cyclopropylamidc, uuuuuuuuu) 4-(2-Pyiidin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid (1 -e hyl-propyll)-amide, vvvwvvvv) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrTolo[ I t2-bJpyrazol-3-yi)- quinoline-7-carboxylic acid ethylamide, wwwwwwwww) 4-{2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l ,2-b]pyrazol-3- yl)-quinoline-7-carboxy1ic acid isobutyl-arnide, xxxxxxxxx) 4-(2-Pyri4in-2-yl-5,6-dihydTO-4H-pyrrolo[l,2-b]pyTa2ol-3-yl)- quinoline-7-carboxylic acid tcrt-buiylainide, yyyyyyyyy) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyTrolo[l ,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid isopropylamidc, ; 7Tm7rr7) 4-(2-Pyr din-2-yl-5,6-dihydro-4H-pytT0lol 1,2-b)pyrazol-3-yl)- quinolinc-7-caiboxylic acid prtipylamidc, aaaaaaaaaa) 4-(2-Pyndin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid (2 mcthyl-butyl)-amidc, bbbbbbbbbb) 4-(2-Pyiidin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid ((l!S)-2-methyl-butyl)-ainide, cccccccccc) 4-(2-Pyiidin-2-yl-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid (2S)-sec-butyiamide, dddddddddd) 4-(2-Pyridin-2-yI-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid (2R>scc-butylamide, cecceeeece) 4-(2-Pyridin-2-y]-5,6-dihydro-4H-pyTTOlo( 1,2-b)pyrazol-3-yl)- quinolinc-7-carboxylic acid -1,2-dimethyl-propyl)-amide, nrrffiT!!) 4-(2-P)Tidin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazo!-3-yl)- quinolinc-7-carboxylic acid (pyridin-4-ylmethyl)-ainide, gggggggggg) 4-(2-P:/ridin-2-yl-5,6-dihydro-4H-pyrTolol 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid (pyridin-3-ylmethyl)-ant' quinolinc-7-carboxylic acid (pyridin-2-ylmcthyl)-amide, iiiiiiiiii) 6-(3-C'uinolin-4-yl-5,6-dihydro-4H-pyTTolo[l,2-b]pyrazol-2-yl)- pyridine-2-carboxylic acid amide, jjjjiiiijj) 1 -(4-Meihyl-piperaztn-1 -yl)-2-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl)-qu>nolin-7-yloxy]-ethanone, kkkxkkkkkk) N-(2-Ditn«hyIamino-eihyl)-2-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pym>lo( 1,2-b]pyrazol-3-yl)-quHnolin-7-yloxy]-acctamide, nilllllli) N-(2-Diinediylamino-ethy1)-N-njethyl-2-[4-(2-pyridin-2-yl-5,6- dihydro-4H-pynrolo{ 1,2-bJpyraz mmmmmmmmmm) N,N-Diinethyl-3-t4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b}pyrazol-3-yl)-quNnolin-7-yIoxy]-benzamide, nnnnnnnnnn) 4-(2-Pyiidin-2-yl-5,6-dihydro-4H-pyrToIo[ 1,2-b]pyrazol-3-yl)- quinoIinc-7-carboxylic acid amide, oooooooooo) 4-(2-Pyiidiii-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-H]pyrazol-3-yl>- quinoline-7-carboxylic acid (2-dimethylamino-€thyl)-mcthyl-amidc, PPPPPPPPPP) 4-(2-Pyiidio-2-yl-5,6-dihydro-4H-pyrrolo( 1,2-H]pyrazol-3-yl)- quinoline-7-carboxylic acid (3"dimethylaTnino-propyl)-mcthyl-amide, qqqqqqqqqq) 4-(2-Pyridm-2-yl-5,6-dihydro-4H-pyrrolo(1,2-H]pyrazol-3-yl)- quino1in«-7.carboxylic acid dimethylamide, nuiuiii) 4-(2-Pyridm-2-yl-5,6-dihydro-4H-pyrrolo( 1 f2-H]pyrazol-3-y1)- quinolin€-7-carboxylic acid nwthylamidc, ssssssssss) 4-{2-Pynd«-2-yl-5,6-dihydro-4H-pyiTolo[ ] ,2-b]pyrazol-3-yl)- quinoline-7-carboxylic acid p>ri uuuuuuuuuu) 2-(6-Mcihyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b}pyrazol- 3-yJ]-quinolinc-6-carboxylic acid (2-dimethylamino-cthyI)-amide, vvvwvwvv) 4-[2- b]pyrazol-3-y]]-quinoIinc-6-carb0xylic acid(3-dimcthylamino-propyl)-amidc, wwwwwwwwww) *l-{2-(6-Methyl-pyridin-2-yl)-5t6-dihydro-4H-pyiTolo[ 1,2- b]pyrazol-3-y|]-quinoline-6-C3rboaiylicacid(2-morpholin~4-yl-cthyl)-amid€, xxxxxxxxxx) 1 [2-(Quinohn-4-yl)-1 -(6-methyl-pyridin-2-y1)-5,6-dihydro-4H- pyTTolo[ 1,2-b]pyrazol-3-yl] quinoHne-7-carboxylic acid N.N-dimethylaminoethylamide, yyyyyyyyyy) 4-[2-(6-M«ihy]pyridin-2-yl)-5,6-dihydro4H-pyn-olo(l,2-bJpyrazol- 3-yl]quinoWne-7-c«rbox-ylic ticid(2-pip€ridin-l-yl-cthyl)aniide, zzz2zzzzzz) N-(2-Dimcthylamino-cthyl)-3-{4-[2-(6-methyl.pyridin-2-yl)-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolin-7-yl}-propionamide, aaaaaaaaaaa) 4-[2-(6-Mcthyl-pyridin-2-yl)-5,6-dJhydro-4H-pyrroloIl,2- b]pyrazol-3-yl]-quinolinc-7-carbo>ylicacid(3-dimc(hylamino-propyl)-ainidc, bbbbbbbbbbb) 4-[2-(6-Methyl-pyridin-2-y!)-5,6-dihydio-4H-pym>lo[1,2- b]pyrazol-3-yl)-quinoline-7-carboji ylic acid (3-pyirolidin-1 -yl-propyl)-amidc, ccccccccccc) 4-t2-(6-Mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2- b)pyrazol-3-yl]-quinoline-7-carbo*ylic acid (3-morpholin-4-yl-propyl)-amide, ddddddddddd)3-{4-[2-(6-Mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyiTolo[l,2- b)pyrazol-3-yl]-quinoIin-7-yl} -propionamidc,, ececcccccee) 4-(2-Pyridin-2-yl-5,6- mrrmTH) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pym>lo[l ,2-bJpyrazol-3-yl)- quinolinc-6-carboxylic acid (2-moipholin-4-yl-clhyl>amidc, Kgggggggggg) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyra2ol-3-yl)- quinoline«6-carboxylic acid, hhhhhhhhhhh) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo( 1,2-b)pyrazol-3-yl)- quinolinc-6-carboxylic acid hydra:ide, iiiiiiiiiii) 4.(2-Pyridin-2-yl-5,6-dihydro-4H-pyiTolo[l,2-b]pyrazoI-3-yl> quinolinc-6-carboxylic acid amide iiiiiUJiiJ) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolinc-6-carboxylic acid (3-mdhylamino-propyl)-amide, kkkkkkkkkkJc) 4-{2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolinc-6-carboxylic acid amide IIIIIIIIIII) 4-(2-Pyridin-2-yl-5,6-dihydro-4H.pyrTolo[l,2-b)pyrazol-3-yl)- quinoline-6-carboxylic acid (2-hydroxy-ethyl)-amide, mmmmmrnrnrtimrnm)4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3- y1)-quinoline-7-carboxylic acid hylrazidc, nnnnnnnnnnn)4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo(l,2-b]pyrazol-3-yl)- qutnoline-7-carboxylic acid hydroxyamide, OCK>OOOOOOOO) 4-(2-Pyridin-2-yl-5, 6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-cart>oxylic acid (2-am no-ethyl)-amide, ppppppppppP)4-(2-Pyrid»n-2-yl-5,6dihydro-4H-pyrrolo[l,2-b)pyra2o|.3-yl)- quinolinc-7-carboxylic acid (2-hydroxy-elhyl)-amide, qqqqqqqqqqq) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrTolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-sulfonic acid amide, iiiiiimn) 4-(2-Pyridin-2-yl-S,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl> quinoline-7-sulfonic acid methylamide, sssssssssss) 4-(2-Pyridm-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinoline-7-sulfonic acid dimethylamide, ttttttttttt) 4-(2-Pyridin-2-yJ-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl> quinoline-7-sulfonic acid (3-dim«hylamiiio-propyl)*amide, uuuuuuuuuuu) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl> quinoline-7-sulfonic acid diethysamidc, ; vvwvwww) 4-(2-Pyridoi-2-yl-516- wwwwwwwwwww) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3- yl)-quinoline-7-sulfonic acid (2-hydroxy-ethyl)-amidc, xxxxxxxxxxx) 4-(2-Pyri(Iio-2-yl-5,6-dihydro-4H-pynolo[1,2-b]pyiBZol-3-yl)- quinolin-7-ylamJne, yyyyyyyyyyy) 2-Dimcthylaniino-A/-[4r(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl)-quinolin-7-yl]-acctamidc, 2Z22Z2Z2ZZZ) 3-Dimcthylamino-N-[4-(2-pyridin-2-yI-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-qumolin-7«yl]propionamide, aaaaaaaaaaaa) N-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo(l,2-b)pyra2ol-3-yl)- quinolin-7-yl]-mcthanesulfonariide, bbbbbbbbbbbb) M -{4-(2-Pyridin-2-y»-5,6-dihydro-4H-pyrrolo( 1,2- b]pyrazol-3-yl)-quinolin-7-yl]-acetamide, cccccccccccc) 4- quinolinc-7-carboxylic acid (2-acelylamino-ethyl)-amide, dddddddddddd) N- {3-(4-(2-Pyridin-2.yl-5,6-dJhydro-4H-pynolo{ 1,2- b)pyrazol-3-yl)-quinolin-7-yloxy]-propyl}-methancsulfonamidc, ceeecceccccc) l-Mcthyl-IH-imidazole-4-sulfonic acid {3-[4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrTolo{l,2-b]pyrazol-3-yl)-quinolin-7-yloxy]-propyI}-amidc, fmrflr/TfO l-(2-DJmethylamino-ethyl)-3-[4-(2.pyridin-2.y|.5t6-dihydro-4H- pyrrolol 1,2-b]pyrazol-3-yl)-quJi»Iin-7-yll -urea, gggfigggggggg) 1 dihydi©-4H-pyrrolo[ 1,2-bJpyraz»I-3-yJ>quino)in-7-yl)-urca, hhhhhhhhhhhh) I pyrrolof 1,2-b]pyrazol-3-yl)-qui»tolin-7-ylJ-urea, *«(«tiiiiaii> (4-(2-Pyridin-2-yf-5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazoJ-3-yI)- quinolin-7-y))-carbamic acid methyl ester, iiiiiiiiijjjt [4-(2-Pyndin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b)pyra2ol-3-yl)- quinoiin-7-yl]-carbamic acid 2-hydroxy-elh>1 ester, kkkJdckkkkJckk) [4 yl)-quinolin-7-yl]-carbamic acid 2-methoxy-ethyl ester, ■ Illlllllllll) 1,3-Bis-[4-(2-pyridin.2-yl-5,6-dihydro-4H-pyrrolo[ 1 ^-bjpyrazoi- 3-yl)-quinoJin-7-yl]-urca, mmmmmmmmmmmrn) Dimethyl-carbamic acid 4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo( 1,2-b]pyraz«»l-3-yl)-quinolin-7-yI ester, nnnnnnnnnnnn) 7-Bromo-2-isopropyl-4-(2-pyridin-2-yl-5,6-dibydro-4H- pyrrolof 1,2-b]pyrazol-3-yl)-quinolinc, oooooooooooo) 2-{4-[2-(6-Methyl-pyridin-2-yI>5,6-dihydro-4H- pyrrolo( 1,2-b]pyrazoJ-3-yJ)-quinolin-6-yl} -propan-2-ol, PPPPPPPPPPPP) 7-C»-Chloro-propyJsulfanyl)-4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-3-ylH*«noline, qqqqqqqqqqqq) 7-Bromo-4-(4-chloro-2-pyridin-2-yJ-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl>-quinoline, ininuifti) 8-ChJoro-4-(2-pyrJdin-2-yl-5,6-dihydro-4H-pyiTolo[ J ,2-b]py»a2ol- 3-yI)-quinolin-7-ol, ssssssssssss) 8-Bromo-4 (2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol- 3-yJ)-quinoIin-7-ol, tttttmtttt) 3-(7-Bromc-quinoIin-4-yl)-2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo{] ,2-b]pyrazol-4-o), uuuuuuuuuuuu) 7-Biomo-4-(4-me(hoxy-2-pyridin-2-yl-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl)-quinoiine, vvvvwvvvvvv) [3-(7-Bromo-quinolin-4-yl)-2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ ] ,2-b]pyra2ol-4-yl]-meihyl-amin€, wwwwwwwwwwww)3(7-Broino-quinolin-4-yl)-2-pyridin-2-yl-5,6-d>hydro- pyrrolo[ 1,2-b]pyrazol-4-one, xxxxxxxxxxxx) 3{4- 3-yl)-quinolin-7-yloxy]-benzamide, yyyyyyyyyyyy) #^-DimcthyW-[4K2-pyridin-2-yl-5,6 777777777777) Dime(hyl-{3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pynrolo[l,2- b]pyrazol-3-yl)-quinol in-7-ylox yj-benzyl} • aminc, aaaaaaaaaaaaa) 4-{2- b]pyrazol-3-yI]-lH-quinolin-2-««K, : bbbbbbbbbbbbb) 4-(2-Pyridin-2-yl-5,6-dJhydro-4H-pynrolo[l^-b]pyra2ol-3- yl)-quinolin-7-ol, ccccccccccccc) 4- (2-(6-Mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo{ 1,2- b]pyrazol-3-yl]-quinolin-7-ol, ddddddddddddd) 6-Mcthoxy-4-(2-pyridin.2-y]-5.6-dihydro-4H-pyiTolot 1,2- b]pyrazol-3-yl)-quinolin-7-ol, cceceeeeeeeee) 3-{4-(2-1)-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl]-quiiiolin-7-yl}-propionic acid methyl ester, fffiYnrffffr) 4-(6-Me0iyl-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol- 3-yl)-quinoline, ggfiggggggeege) 3- (4-{2-(6-Meihyl-pyridin-2.yJ)-5,6-dihydro-4H- pyrTolo[l,2-b]pyrazol-3-yl]-qui«olin-6-yl}-propionic acid methyl ester, hhhhhhhhhhhhh) 7-Amino-4-(2-(6-Mcthyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl]-quiaoline, iiiiiiiiiiiii) N,N-Dimethyl-3-{4-[2-(6-methyi-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo( 1,2-b]pyrazo1-3-yl]-quii»Hn-7-yl}-propionamide, JiiUJjjjjjjj) N- (3-[4- ylVquinolin-T-yloxyj-propylJ-acelamide, kkkkkkkkkkkkk) N Acetyl-N-{4-[2-(6-methyI-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazol-3-yl]-qui»olin-7-yl}'acetamide, lllIllllJllll) 2-Pyridin-2-yl-3-quinolin-4-yI-pyrazolo[l,5-a]piperidin-7-ol, mmmmmmmmmmmmm) 7-Acctoxy-2-pyridin-2-yl-3-quinolin-4-yl- pyrazolo[ 1,5-a)pipcridine, nnnnnnnnnnnnn) Methyl- {3-f4-(2-pyridin-2-yl-5,6-dihydro-4H-pyiTo!o[ 1,2- b]pyrazol-3-yl)-quino)in-7-yloxy]-propyl}-amine, ooooooooooooo) 7-(Piperidin-4-yloxyH-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazoi-3-yl)-qi)iinoline, ppppppppppppp) 4^2-(6-McthyI-pyridin-2-yl)-5,6-dihydra-4H-pyiTolo[l ,2- b]pyrazol-3-yl]-quinoline-7-caiboxylic acid (2-amino-l .l-dimcthyl-ethyl^amidc, qqqqqqqqqqqqq) {6-(3- b]pyrazol-2-yl]-pyridin-2-yl}-tiKthanol, iniiiimiu) [6-(3-Quinolin-4-yl-5,6-d Jhydro-4H-pyrroio[ J ^-b]pyra2o1-2-yl)- pyridin-2-yl]-mcthanol, sssssssssssss) 4-[2-(6-(neihyl-pyridin-2-yl)-5,6-dJhydro-4H-pyrrolo[l,2- b]pyrazol-3-yl]-phenol, nnmntttt) 7-( I -Mcthyl-pyiTolidin-3-ylmcthoxy)-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrro!o[ 1,2-b]pyr*zol-3-yl)-quinolinc, uuuuuuuuuuuuu) 7- dihydro-4H-pyrrolo[ 1,2-b]pyi*»>M-yO-quino!ine, vvvvwvvvww) 4-{2- b]pyra2ol-3-yl]-quinoline-7.cai*ootylic acid(2-dimethylamin6-1,1 -dimcthyl-eihyl>amide, wwwwwwwwwwwww) (5)-(3-2-(6-inethyl-pyridin-2-yl)- 5,6-dihydro-4H-pyrrolo[ 1,2-b]pyiaiol-6-yU-incthanol, xxxxxxxxxxxxx) («>.{3-(4-Fluoro-phcnyl)-2-(6-methyl-pyridin-2-yl)-5,6- dihydro-4H-pyrrolo[ 1 ^-bJpyraaol-^-yn-nwthanol, yyyyyyyyyyyyy) (,sH3-(4-Fi|io'ro-PhenyJ)'2-(6-methyl*pyr' dihydro-4H-pyrrolo[ 1,2-b]pyraiol-6-yl]-acetonitrile, zzzzz2Z2zzzzz) (^H3- dihydro-4H-pyn-olo[l,2-b]pyra«>l-6-yI]-acetonitrile, aaaaaaaaaaaaaa) 4 y])-quinoline, bbbbbbbbbbbbbb) 4 quinolinc, cccccccccccccc) 3(4-(2-Pyridin-2-y!-5,6-dihydro-4H-pyirolo[I^-b)p)razol- 3-yl)-quinolin-7-yl}-oxazo)idin-2-one, dddddddddddddd) I [4-(2-Pyridin-2-y!-5,6-dihydro-4H-pyTrolo{lr2b]pyra2oi- 3-yl)-quinolin-7-yl]-imidazolidm-2-one, cccecceeeeeecc) 4 yl)-7-(pyridin-4-ylinethoxy)-quiK>linc, ffiTimrfrfnO 4- pyridin-3-yl-propoxy)-quinolin«:, KBgegggggggggg) 7- (4,5-Dihydro- \ H-imidazol-2-yl)-4-(2-pyridin-2-yl-5*6- dihydro-4H-pyirolo( 1,2-b]pyra2ol-3-yl)-quinolinc, hhhhhhhhhlihhhh) 4-[5-(4-F)uoro-phcnyl)-2-(6-mcthyl-pyridin-2-yl)-5,6- dihydro-4H-pyrrolo[l ,2-b]pyra2oI-3-yl]-quinolinc (Enantiomer A), iiiiiiiiiiiiii) 4-[5-(4-Fluoro-phenyl>2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo{ 1 ^-b]pyrazol-3-yl]-quinolinc (Enantiomer B), jjjijuiiijiiijj) 2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo(5,l-c]mofpholinc, kkkkkkkkkkkkkk) 4-[2- b]pyrazol-3-yl]-quinoline, . IIIIHIHIIII!) 3-{4-{2-( mmmmmmnimmmmmrfim) 7-(6-Methyl-pyridazin-3-yloxy)~4-(2-pyridin-2-yl- 5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, nnnnnnnnnnnnnn) 4-{2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-bJpyrazol-3- yl)-7-(4-(4-pyriinidin-2-yl-pipcrazin-l-yl)-butoxy3-quinolinc, oooooooooooooo) 7-[3-[4-(2-Methoxy-phenyl)-pipcrazin-l-yI]-propoxy}-4- (2-pyridin-2- yl-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3-yl)-quinoline, PPPPPPPPPPPPPP) Py ridin-2-yI- {3-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyiTolof 1,2-b]pyrazol-3-yl)-quinolin-7-ylo*y]-propyl}-amine, qqqqqqqqqqqqqq) 4-| 2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrok>[ \ ,2- b]pyrazol-3-yl]-quinoline-7-carboxylic acid (2-dimethyiamino- J -methyl-ethyl)-amidc, uiiTiiniiiii) 4-[2-(6- VfethyI-pyridin-2-yl)-S,6-dihydro-4H-pyrrolo( 1,2- b}pyrazol-3-ylJ-quinolinc-7-carboxylic acid amide, ssssssssssssss) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolinc-7-carboxylic acid (3 dimethylamino-propyl>amidc, uutntmttt) 4-(2K6-Methyl-pyridin-2-yl>5,6-dihydro^H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline-7-carboxylicacid(2-dimcthylamino-ethyl)-methyl-ainide, uuuuuuuuuuuuuu) N,N-Dimcthyl-3- {4-[2- dihydro-4H-pyrro1o( 1,2-b]pyrazol-3-yl]-quinoKn-7-yI}-acrylamide, vvwvvvvvvvvw) *-{2-Pyridin-2-yl-5>6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl)-quinoline ]-oxide, wwwwwwwwwwwwww) 7-Benzyloxy-4-(2-(6-mclhyl-pyridin-2-yl)-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrjtzol-3-yl]-quinoline, : xxxxxxxxxxxxxx) ♦-(2-olo loro-pyridin«2-yl)-5 [1,2-b]pyrazo]-3-yl]-quinoline, yyyyyyyyyyyyyy) (>-(3-Quinolin-4-yl-5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazol- 2-yl)pyridine-2-carboxylic acid methyl ester, zzzzzzzzzzzzzz) ^K7-Chloroquinolin-4-yl)-3-(pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[l ,2Db]pyrazole, aaaaaaaaaaaaaaa) *- yl)-quinoline, bbbbbbbbbbbbbbb) 3 - {4-[2-(6-Mcthyl-pyridin-2-yl)-5,6^ihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl]-quinoIin-6-yl}-acrylic acid methyl ester, ccccccccccccccc) 4~(2-(2-Methyl-thiazol-4-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-yl]-quinoline, ddddddddddddddd) 3-(4-Fluoro-phenyl)-2-(2-methyl-thiazoI-4-yl)-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazole, eeeceeeceeeeeec) 4-(2-(2-Methyl-2H-pyrazol-3-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazoI-3-yl]-quinoline, fffffffffffffTO 4-(2-Thiazol-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)- quinoline, ggggegggfiggeegg) "•[2-(l-Methyl-lH-imidazol-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl]-quinoline, hhhhhhhhhhhhhhh) 6/f-DichIoro-4-[2-(6-methyi-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ l,2-b}pyrazol-3-yl)-qumoline, iiiiiiiiiiiiiii) (S)-6-Bcn2yloxymcthyl-3-(4-fluoro-phenyl)-2-(6-methy1-pyridin- 2-yl)-5,6-dihydro-4H-pynolo[ 1,2-b]pyr azoic, iiiiiiiiii^lip N,N-Dim and the pharmaceutical! y acceptable salts, esters ffflfVpniHintg* thercoOU 6. A compound as claimed In claim 2, wherein the compound is selected from the group comprising: a) 7-mcthoxy-4-(2-i>yridin-2-yl-5,6-dihydro-4H-pyrrolol 1,2-b]pyrazol-3-y1)- quinolinc, b) 7-benzy]oxy-6-methoxy-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrTOlo{ 1,2- bJpyrazol-3-yl)-quinoline c) 7-Bromo-4-[2-{6-inethyI-pyridin-2-y()-5,6-d ihydro-4H-pyrTolo{ 1.2- b]pyrazol-3-yl)-quinoline d) 7-Methoxy-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyirolo[l,2- b]pyra2ol-3-y!]-quinoUnc c) [3-(7-Bromo-quinolin-4-yJ)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo( 1,2-bJpyrazol-6-yl]-mei;hanol 0 4-(7-Bromoqui5alin-4-yJ)-:i-(pyTidin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2- bjpyrazole g) 4-(7-Chloro-qui!tolin-4-yl)-3-(6-methylpyridin-2-yl)-5,6-dihydro-4H- pyrroJo[ ] ,2-b]pyrazole, h) 6,7-Diftuoro-4-[ 2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrToJo[ J ,2- b]pyrazol-3-yl]-quinoline, i) 6,7-Dimcthoxy-4-[2-(6-methyl-pyridin-2-yl>5,6-dihydro-4H-pyfTolo{ \ ,2- b]pyrazol-3-y|].quinolin« j) 4-[2-(6-Mcihyl- (jyridm-2-yO-5,6-dihydro-4H-pyrrolo( 1,2-b)pyrazol-3-yl]- quinolinc-7-carboxylic acid methyl ester k) Dirnelhyl- {3-(4 yl)-quinolin-7-yloxy]-propyl}-jmine, 1) {3-(6-methox:y-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazol-3- yl)-quinolin-7-yloxy]-propyl f-dimcthyl-amine, m) Cyclopropylnrieihyl-propyl- {3-I4-(2-pyridJn-2-yl-5,6-dihydro-4H- pyrro)o[ 1,2-b]pyTa2ol-3-yl)-t|uinolin-7-.vloxy]-propyl}-amine, n) Diethyl- {3-{4 (2-pyridin-2-yl-5,6-dihydro-4H-pynolo[ 1,2-b)pyrazol-3-yl)- quinolin-7-yloxy]-propyl} -ainine, « o) Ethyl-methyl- {3-[4-(2-pyridin-2-yI-5,6-dihydro-4H-pyrrolo{ 1,2-b]pyra2ol- 3-yl)-quinolin-7-yloxy]-propy1}-aminc, P) 3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrroIo[ 1,2-b)pyra2ol-3-yl)-quinolin- 7-yloxy]-propytamine, q) 7-[3-(4-mcthjl-pipcra2in-1 -yl)-propoxy]-4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrro1o( 1,2-b]pyra2ol-3-yl)-quinolinc, r) B€n2yl-methyI-{3-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyiTolo(l,2- b]pyrazol-3-y|)-quinolin-7-yloxy]-propyU-amine, s) 7- pyrrolo[ 1,2-b]pyrazol-3-yl)-quino!ine, 0 4-{2-pyridin- 2-yl-5,6-dihydro-4H-pyrrolo{ J ,2-blpyrazo1-3-yO-7-(3- pyrrolidjn-1 •yl-propoxy)-quinoline, u) 7-{3-azepan- -yI-propoxy)-4^(2-pyridin-2-yl-5,6-dihydro-4H-pyrTolo[l,2- b]pyrazoJ-3-y|)-quinolinc, v) 7-(3-imidazol-l-yl-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pynrolo[l,2-b]pyrazoJ-3-yl)-quinoline, w) 7-(3-pyrazol-1 -yI-propoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo( 1,2- b]pyrazol-3-yl>quinolinc, x) ]t-{3-[4-(2-p)aidin-2-yl5,6-dJhydro-4H-pyrTololl,2-blpyra2ol-3-yl)- quinolin-7-yloxy]-propyI} -(1,4*)bipipcridinyl, y) Cyclopropyl( 1 -mcthyl-pipcridin-4-yl)- {3-[4- 4H-pyrTolo[ 1,2-b]pyrazol-3 yl>quinolin-7-yloxy]-propyl}-amine, 2) 4-(2-pyridin- 2-yl-5,6-dihydro-4H-pyn-oIo( 1,2-b]pyTazol-3-yl>7-(3- [I,2,3]tria2ol-l-yl-propoxy)-quinoline, aa) Dimethyl-(3 {4-[2-(6-methyl-pyridin-2-y!)-5,6-dihydro-4H-pynolo[ 1,2- b]pyrazol-3-yI]-quinolin-7-yloxy}-propyI)-amine, bb) Dicthyl-(3- {4-[2 (6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l ,2- b]pyrazol-3-yl]-quinolin-7-yloxy}-propyl)-amine, cc) CyclopropylmcihyK3-{4-(2-{6-meihyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl]-qui«olin-7-yloxy) -propyl)-propyl-amine, dd) Ethyl-mcthyl-5,6-dihyd«>-4H- pyrro)o[ 1 ^-b]pyrazol-3-yl]-quinolin-7-yloxy}-propyl)-amin€, ce) Dimcthyl-{2-[4-{2-pyridin-2-yl-5,6-dihydro-4H-pym>Io[lt2-b]pyra2ol-3- yl)-quinolin-7-yloxy)-ethyl} -aniinc, fl) Dieihyl- {2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b)pynaol-3-yl)- quinolin-7-yIoxy)-ethyl)-amiiK, 88) 7-(2-piperidin-l yi-ethoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l ,2- b]pyrazol-3-yl)-quinolinc, hh) Ethyl-methyl- {2 -{4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo(l ^-b]pyrazol- 3-yl)-quinolin-7-yloxy]ethyl} -umine, ii) 4- pyrro)idin-l-yl-cthoxy)-quinol nc, JLJ) 7-[2-(4-mcthyi-pipcrazin-l-yl)-cthoxy]-4-{2-pyridin-2-yJ-5,6-dihydro-4H- pyrrolof! ,2-b]pyrazol-3-yl)-quinoline, kk) Dimethyl-{3-[I-oxy-4-(2-pyridin-2-y]-5,6-dihydro-4H-pyrrolo[l,2- bJpyrazol-3-yl)-quinolin-7-ylony]-propyl}-amine, H) 7-Methylsulfan/)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo(l,2-b3pyrazol- 3-yl)-quinolinc, mm) 7-Ethylsulfanyl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrTolo[l,2-b]pyra2ol- 3-yl)-quinoline nn) 7-Benzylsulfanyl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yl)-quinoline, oo) 3>[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo{ 1,2-b]pyrazol-3-yl)-quinolin- 7-ylsulfanylJ-propan-l -ol. pp) Dimethyl- {2-[* -(2-pyridin-2-yl-5,6-dihydro-4H-pyTTolo(1^-b]pyrazol-3- yl)-quinolin-7-ylsulfanyl]-ethyl}-amine, qq) 7-(2-Propoxy-«tho>y)-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2- 3]pyrazol-3-yl )-quinoline rr) 3- {3-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrro!o( 1,2-b)pyrazo1-3-yl)- quinolin-7-yloxy)-propyl}-oxazolidin-2-one, ss) 1 - {3-[4-(2-PyrJdin-2-yl-5,6-dihydro-4H-pynrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-propyl}-imidazolidin-2-one, tt) 3- {3-(4-(2-Pyridin-2-yl-S,6-dihydro-4H-pyrTolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-propyl) -3H-benzooxazol-2-one, uu) 2- {3-l'4-(2-Pyridin-2-yl-5,,6-dihydro-4H-pyiTolo[ 1,2-b]pyrazo!-3-yl)- quinolin-7-yloxy]-propyl} -isoindole-1,3-dione, vv) 7-(3-Fluoro-propoxy)-4-(2-pyridtn-2-yI-5,6-dihydro-4H-pyiToIo[ 1,2- blpyrazoI-3-yl)-quinolinc, ww) 7-(3-Chloro-p opoxyH-l^-pyridin2-yl-5,6-dihydro-4H-pynoloI 1,2- b]pyrazol-3-yl).quinoline, xx) 7-(3-chIoro-piopoxy)-6-methoxy-4-(2-pyridin-2-yI-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyra2ol-3-yl)-quinoline, yy) 7-(3-chloro-propoxy)-4-[2-(6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyra2ol-3-yl]-quinoHne, zz) (1 - {3-[7-(2-chloro-ethoxy)-quinoIin-4-yl]-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-2-y|} -propenyl)-niethylcnc-amine, aaa) N,N-Dicthy1-2-[4-{2-pyridin-2-yl-5t6-dihydro-4H-pynx)lo[l,2-b]pyrazol- 3-yl)-quinolin-7-yloxy]-acetamidct bbb) 7-[2-((2R> 1 • Methyl-pynolidin-2-yl)-€thoxyH-(2-pyridin-2-y!-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-qumolinc, ccc) 7-( 1 -Mcthyl-piperidin-3-ylmcthoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl> quinoline, ddd) 7-(3-N,N-Dimethyiamino-2-methyl-propyloxy)-4-(2-pyridin-2-yl-5,6- d ihydro-4H-pyrrolo[ 1,2-b](»yrazol-3-yl)-quinolinc, eec) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolot 1,2-b]pyrazol-3-yl]- 7 -propoxy-quinolinc, ffO {4-[2-(6-Me thyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3- yl]-quinolin-7-yloxy}-acetic acid methyl ester, ggg) 7-lsopropo> y-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyTTolo[ 1,2- b]pyra2ol-3-y|).quinoline, hhh) 4-(2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrro)o[l,2-b]pyra2ol-3-yl]- 7-(3-morpholin-4-yl-propoxy)-Quinoline, iii) 7-Benzyloxy-2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo[ 1,5-a]piperidine, jij) 2-[4-(2-pyridin-2 -yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoJin-. 7-yloxy]-acetatnide, kkk) 7-(5-Phenyl-[ 1,2,4]oxadiazolO-ylmcthoxyH-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrTOlo[ 1,2-b]pyrazol-3-yl>quinolinc, HI) 7-(2^-Difluoro«benzo[l,3]dioxol-5-yImcthoxy)-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[! ,2-b)pyrazol-3-yl)-quinoline, mmm) 7-[2-((25)-1 -Mcthyl-pyrrolidin-2-yl)-cthoxy)-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyra2ol-3-yl)-quinoline, nnn) 5-[4- 7-yloxymclhyl]-pyrrolidin-2-oiH:, ooo) 7-( I -Mcthyl-pipendin-2-ylincthoxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo(l,2-b]pyrazol-3'yl)-quino!ine hydrochloride, PPP) 7-[2-{ 1 -Methyl-pyrrolidin-2-yl)-cthoxy]«4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrro)o[ 1,2-b]pyrazo)-3-yl)- rrr) 7-Methanesulfonyl-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazoI-3-yl)-quinoline, sss) 7-Ethanesulfonyl"4-(2-pyridin-2-y]-5,6-dihydro-4H-pyrrolo[ 1,2-b)pyrazol- 3-yl)-quinoline, ttt) 4-(2-Pyridjn-2-yl-5,6-dihydro-4H-pyiTolo[l,2-b)pyrazol.3-yl)-7-[3- (pyrimidine-2-sulfonyl)-propoxy|-quinoline, uuu) 7-[3-( I -McthyI-lH-imidazole-2-suIfony])-propoxy]-4-(2-pyridin-2-yl-5,6- dihydro-4H-pynolo[ 1,2-b)pyraz€il-3-yl)-quinolinc, vvv) 7-[3-(4-Chloro-benzenesulfonyl)-propoxy]-4-(2-pyridin-2-yJ-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- www) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyTazol-3-yl)-7-[3- (pyridin-2-ylnr»ethanesulfonyl)-propoxy]-quinolinc, xxx) 4-(2-Pyridin-2-y|-5f6-dihydro-4H-pyrrolo(J,2-b]pyra2ol-3-yI)-7-(3- (pyridin-2-ylmcthanesulfinyl)-pn)poxy]-quinolinc, yyy) 3- {4-[2-(6-Methyi-pyridin-2- yl>5,6-dihydro-4H-pyrrolo{ 1,2-b]pyrazol-3- yl]-quinolin-7-yl}-acrylic acid methyl ester, 222) 4-[2-(6-Methyl-pyridin-2-yl)"5,6-dihydro-4H-pyTToIo[ J ,2-b]pyrazol-3-yl]- 7-vinyl-quinoline, aaaa) 3-{4-[2-(6-Mcihylpyrdin-2-yl-5,6-dihydro-4H-pyiTolo[I,2-b]pyrazol-3- yl]quinolin-7-yl}-I -piperidin-1-yl-propenonc, bbbb) 7-Bcn2yl-4-[2-(6-inethyI-pyridin-2-yl)-5,6-dihydro-4H-pyn-oIolJ,2. b)pyrazol-3-yI]-quinol ine, cccc) 4-[2-(6-M"cthyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo(l^-bJpyrazol-3-yl]- quinolinc-7-carboxylic acid, : dddd) 3-(4-{2-(6-Methyl pyridin^-yl^S^-dihydTcMH-pyrrolofl^-bJpyrazol-3- yl]-quinolin-7-yl) -acrylic acid, eeee) 3- {4-[2-(6-Mcthyl pyridin-2-yl)-5,6-dihydro-4H-pynrolo( 1,2-b)pyrazol-3- yl]-quinolin-7-yl}-propionicacid, ftTf) 4-(2-Pyridin-2-yl-.',6-dihydro-4H-pyrrolo[l ,2-b]pyrazol-3-yl)-quinoline-7- carboxylic acid cyclopentylamidc, gggg) 4-(2-Pyridin-2-yl-! ,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazpl-3-yl)-quinolioe-7- carboxylic acid (2-morpholin-4-yl-ethyl)-amide, hhhh) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)-quinoline-7- carboxylic acid [2-(lH-imidazoI-A-yl)-cthyl]-amide, iiii) 4-(2-Pyridin-2-yl-3,6-dihydro-4H-py«Tolo[ 1 ^-b)pyra2ol-3-yI)-quinoJine-7. carboxylic acid (2-methylamino-e(hyl)-ainide, jiij) 4-{2-Pyridin-2-yI-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoHne-7- carboxylic acid (3-methylamino-piopyl)-aiiiide, kkkk) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b}pyrazol-3-yl)-quinoline-7- carboxylic acid (2-dimethylamina-€thyl)-amidc, 1111) (4-Methyl-pipcrazin-l-yl)-[4H;2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2- b]pyrazol-3-y))-quinolin-7-yl]-meirhanone, mmmm) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrTolo(l ,2-b]pyrazol-3-yI)- quinoline-7-carboxylic acid cyclobutylamide,, nnnn) 4-(2-Pyridin-2-yl -5,6-dihydro-4H-pyrrolo(1,2-b]pyrazol-3-yl)-quinoline-7- carboxyfic acid cyclopropylamkle, oooo) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline«7- carboxyiic acid (l-ethyl-propyl)-amide, PPPP) 4-(2-Pyridin-2-yf-5,6- qqqq) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pynrolop ,2-b]pyrazol-3-yl)-quinoline-7- carboxylic acid isobutyl-amide mr) 4-(2-Pyridin-2-> l-5,6-dihydro-4H-pym>lo( 1,2-b)pyn«ol-3-yJ)-quJnoHne-7- carboxylic acid tert-butylamidt, ssss) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo(l,2"b]pyra20l-3-yI)-quinolinc-7- carboxylic acid isopropylamide, ««) 4~(2-Pyridin-2- /l-5,6-dihydro-4H-pyrrololl ^-bJpyrazol-S-yO-quinoline-?- carboxylic acid propylamidc, uuuu) 4-(2-Pyridin-2-yJ-5,6-d vwv) 4-(2-Pyridin-2 yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolinc-7- carboxylic acid ((2S)-2-mcth,vl-botyJ>aroide. wwww) 4-(2-P widin-2-yI-5,6-d>hydro-4H-pyTrolo[ 1,2-b]pyTazol-3-yl)- quinolinc-7-carboxylic acid (2S)-scc-b«)iylamidc, xxxx) 4^2-Pyridin-2-y!-5,6-dihydro-4H-pyrroJo[ 1,2-b]pyrazoI-3-yl>-quinoIinc-7- carboxylic acid (2R)-sec-buty!amide, yyyy) 4-(2-Pyridin-i -yJ-5,6-dihydro-4H-pynro)o( 1,2-b]pyrazol-3-yl>quinoHne~7- carboxylic acid ((IR)-1,2-diriiethyl-piopyl)-amide, 2222) 4-(2-Pyridin-:.'-yN5,6'dihydro-4H-pyrro?of 1,2-b]pyra2ol-3-yl)-quinolinc-7- carboxylic acid (pyridin-4-y!mcthyl)-amidc, aaaaa) 4-(2-Pyrtdin- 2-yi-5,6-dihydro-4H-pyrrolof 1,2-b]pyra2Ol-3-yl)-quinoline-7- carboxyh'c acid (pyridin-3-yimeihyl)-amide, bbbbb)4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyTTolo[l,2-b]pyrazol-3-yl)-quino)inc-7- carboxylic acid (pyridin-2->Ime«hyl)-amide, ccccc) l-(4-MeihyI-pipera2in-l-yI)-2-(4-(2-pyridin-2-yI-5,6-dibydro-4H- pyrrolof 1,2-b3pyrazol-3-yJ)-quinoHn-7-yloxy]-ethanone, ddddd)N-(2-dimeihylamino-ethyl)-2-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yI)-quir«oiin-7-yloxy]-acetamide, eeeee) N-(2-dimcthylamino-cthyl)-N-methyl-2-[4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-3-yl>qginolin-7-yloxy)-acetamidc, fffTif) N.N-Dimeihyl-3 (4-(2.pyridin-2-y!-5,6-dihydro-4H-pyiTolo(1,2-b]pyrazol- 3-yl)-quinolin-7-yloxy]-bcnzarnidc, ggggg) 4-(2-Pyridin-2-yi-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-y1)-quinoline-7- carboxylic acid amide, hhhhh) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo{ 1,2-H]pyrazol-3-yl)-quinoUnc- 7-carboxylic acid (2-dimethylamino-eChyljhmethyl-amide, iiiii) 4-(2-Pyridin-2->l-5,6-dihydro-4H-pyTTolo[l,2-H)pyrazol-3->i)-quinoline- 7-carboxylic acid (3-dimethyia,nino-propyl)-methyl-amide, : jijjj) 4-(2-Pyridin-2-j'1-5,6-dihydro-4H-pyrrolo[ 1,2-H]pyrazol-3-yl)-quinoline- 7-carboxylic acid dimcthylamiie, kkkkk) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrroloI 1,2-H]pyrazol-3-yl)-quinolinc- 7-carboxylic acid mcthylamidi:, 1111!) 4-(2-Pyridin-2- /l-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quino!ine-7- carboxylic acid pyridin-2-yIanudc, mmmmm) 1 -[2- pyrrolo( 1,2-b]pyrazol-3-yll qt inoline-7-carboxyiic acid N.N-dimcthylaminocthylamidc, nnnnn) 4-[2- yl]quinolinc-7-carbox-yIic acid (2-pipcridin-l-yl-ethyI)amidc, ooooo)N-(2-Dimethylamino-cthyl)-3-{4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro- 4H-pyTTolo(l,2-b]pyrazol-3-yl]-quinolJn»7-yl}-propionatnidc, ppppp) 4-{2- quinoline-7-carboxylic acid (J-dimcthylamino-propyl)-amidc, qqqqq)4-{2-(6-Mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyiroJo[l,2-b]pyrazol-3-yi]- quinoline-7-carboxylic acid (J-pyrrolidin-l-yl-propyl)-amide, mn) 4-[2-(6-Meth>l-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo(l,2-b]pyrazol-3-yn- quinolinc-7-carboxylic acid (3-morphol«n-4-yl-propy1)-amide, sssss) 3-{4-(2-(6-M«uhyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo(l,2-b]pyrazol-3- yl]-quinolin-7-y|)-propionamide, UtM) N-(2,2-Dime«hyl*mino-ethyl)-N-methyl-3-{4-[2-(6-methyl-pyridin-2-yl)- 5,6-dihydro-4H-pyrrolo[l,2-b]p)Tazol-3-yl]-quinolin-7-yJ}-propionamide, uuuuu) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrroIo[ 1,2-b]pyra2oJ-3-yJ>-quinoline-7- carboxylic acid hydrazidc, wvvv) 4-(2-Pyridin-2-yl- 5,6-dihydro-4H-pyrTolo[ 1,2-b]pyrazol-3-yl)-quinoline-7- carboxylic acid hydroxyamide, wwwww) 4-(2-Pyrid«n-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyra2ol-3-yl)- quinolinc-7-carboxylic acid (2-amino-ethy|)-amide, xxxxx) 4-(2-Pyridin-2-yJ- 5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazoJ-3-yl)-quinoJine-7- carboxyJic acid (2-hydroxy-ethyl>amide, yyyyy) 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pynrolo[] ,2-b]pyrazol-3-yl)K|uinolinc-7- sulfonic acid amide, Z2222) 4-(2-Pyridin-2-yl-.*),6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3-yl}-quinolinc-7- sulfonic acid mcthylamidc, aaaaaa)4-(2-Pyridin-2-y]-."i,6-dihydro-4H-pyrToIo(l,2-b]pyrazol-3-yl)-quinoline-7- sulfonic acid dimcthylamide, bbbbbb) 4-(2-Pyridi i-2-yl-5,6-dihydro-4H-pyrrolo(; ] ,2-b]pyrazol-3-yI)- quinoline-7-sulfonic acid (3-dimeihylamino-propyl)-amide, cccccc)4-(2-Pyridin-2-yl-5,6-dihydro-4H-pynrolo[ 1,2-b]pyrazoJ-3-yl)- sulfonic acid diethylamide, dddddd) 4-(2-Pyriditi-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl>- quinoline-7-sulfonic acid (2-pipendin-l-yl-ethyl)-amide, cceccc)4-(2-Pyridin-2-yl-5 (6-dihydro-4H-pyrTolo[ 1,2-b]pyrazoI-3-y!)-quinoh"ne-7- sulfonic acid (2-hydroxy-ethyl)-aniidc, ffTTIflf) 4-(2-Pyridin-2-yJ-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3-yl)- ggggfig) 2-DimcthyIamino-A^-{4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo( 1 »2-b]pyrazol-3-yl)-quinolin-7-yl]-acetainide, hhhhhh) 3-Dimcthylamino-N-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolin-7-yl]propionamide, iiiiii) N-[4-(2-Pyridin-2->l-5,6-dihydro-4H-pyrrolo[l,2-b)pyrazol-3-yl)- quinolin-7-yl]-methanesulfonamid JMJ) N-[4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-3-yl)- quino!in-7-yl]-acetamide, kkkkkk) 4-(2-Pyridin-2-yl-S,6^ihydro-4H-pyTTolo{1,2-b)pymol-3-yl)- quinoline-7-carboxy)ic acid (2-acctylamino-ethyl)-amide, 111111) N-{3-[4-(2-Pyridin-2-yl-5.6-dlihydro.4H-pyrrolotl,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-propyl}-methanesulfonarnide, mmmmmm) 1 -methyl-1 H-imidazole-4-sulfonic acid {3-{4-(2-pyridm-2-yN5,6- dihydro-4H-pyrrolo[ 1,2-b]pymol-3-yl)-quinolin-7-yloxy]-propyl}-ainidef nnnnnn) I •(2-Dimcthylamino-ethyl)-3-t4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolin-7-yl]-urea, oooooo) 1 -(3-Dimcthylamino-propyl)-3-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolo[l,2-b]pyrazo1-3-yl)'qainolin-7-yl]-urca, ; PPPPPp) 1 -(2-H ydroxy-cthyl)-3-[4-(2-pyridin-2-yl-5,6-dihydro-4H- pyuolo{ ] ,2-b]pyTazol-3-yl)-quinolin-7-yl}-urea, qqqqqq) [4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyiTolo[l,2-bJpyra2ol-3-y))- quinolin-7-y|]-carbamic acid methyl ester, mrrr) [4-(2-Pyridin-2-yl-5,6- ssssss) [4-(2-Pyridin- 2-yl-5,6-dihydro-4H-pyTTolol 1,2-b]pyrazol-3-yl)-quinolin-7- yl]-carbamic acid 2-methoxyethyl ester, ttmt) 1 ,3-Bis-[4-(2- pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b}pyrazol-3-yl)- quinolin-7-yl)-urca, uuuuuu) Dimethyl-carbamic acid 4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrTolo[ 1,2-b]pyrazol-3-yl)-quinolin-7-yl ester, vvvvvv) 7-Broino-2-isopropyl-4-(2-pyridin-2-yl.5,6-dihydro-4H- pyrrolo[ 1.2-b}pyrazoi-3-yl)-quinoHoe, wwwwww) 7-(3-Chloro-propylsulfanyl)-4-(2-pyridin-2-yl-S,6-dihydro-4H- pyrrolo[ 1,2-b)pyrazol-3-yl)-tjuinoline, xxxxxx) 7-Bromo-4-(4-chloro-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazol-3-y|)-quinoline, yyyyyy) 8-Chloro-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol- 3-yl)-quinolin-7-ol, zzzzzz) 8-Bromo-4(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol- 3-yI)-quinolin-7-ol, aaaaaaa) 3-(7-Brotmo-quinolin-4-yl)-2-pyTidin-2-yl-5,6-dihydro-4H- pyrrolot 1,2-b)pyrazol-4-ol, bbbbbbb) 7-Bromo-4-(4-melhoxy-2-pyridin-2-yI-5,6-dihydro-4H- pyrrolo( 1,2-b]pyrazol-3-yl)-quinaKne, ccccccc) (3-(7-Bromo-quinolin-4-yl)-2-pyridin-2-yl-5,6-dihydro-4H- pyrTolo[ 1,2-b]pyrazoI-4-yl )-mcthyl-aminc, ddddddd) 3-(7-Bronio-quinolin-4-yI)-2-pyridin-2-yi-5,6-dihydro-pym)lo[ 1,2- b)pyrazol-4-onc, ceeeeee) 3-[4-(2-P)fidin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-yloxy]-benzamide, fffffff) N,N-Dimethyl-3-|4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrololl,2-b)pyrazo1- 3-yl)-quinolin-7-yloxy]-thiobcnzamidc, ggggggg) Dimethyl{3-(4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2- b]pyrazo!-3-yl)-quinolin-7-yloxy]-benzyl}-amine, hhhhhhh) 4-(2-Pyri«lin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-ol, iiiiiii) 4-(2-(6-MethyI-pyridin-2-yl)-5,6-dihydro-4H-pynro!o[ 1,2-b]pyrazol-3-yl]- quinolin-7-ol, jjjjjjj) 6-Methoxy-4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)- quinolin-7-ol, kkkkkkk) 3- i4-[2-(6-Mcthy|.pyridin-2-y1)-5,6-dihydro-4H-pyrrolo[l ,2- b]pyrazol-3-yl)-quinolin-7-yl}-propionic acid methyl ester, IIIIIII) 7-Amino-4-[2-(to-Mcthyl-pyridin-2-yl)-5,6-dihydro-4H-pyfTolo( 1,2- b]pyrazol-3-y|]-quinoIinc, mmmmmmm)N,N-Dinielhyl-3-{4-t2-(6-mcthyl-pyridin-2-yl)-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazol-3-yl]-qu»nolin-7-y|} -propionamidc, nnnnnnn) N- yl)-quinolin-7-y|oxy]-propyl}-acciamide, ooooooo) N-Acctyl-N- {4-{2 pyTrolo[l,2-b]pyrazol-3-yl]-quinoHn-7-yl}-acetamide, ppppppp) 2-Pyridin-2-yl-3-quinolin-4-yl-pyrazolo( 1,5-a]piperidin-7-ol, qqqqqqq) 7-Acetoxy-2-pyridin-2-yl-3-quinolin-4«yl-pyrazolo[l,5- a]piperidine, rnrmr) Methyl- {3-[4-(2-pyridin-2-yI-5,6-dihydro-4H-pynrolo[ 1,2-b]pyrazol-3-yI)- quinolin-7-yloxy]-propyl}-amine, sssssss) 7-(Piperidm-4-yloxy)-4-(2-pyridin-2-yl-5,6-dihydro-4H- pyrrolof 1,2-b]pyrazoU3-yl)-quinolinc, ttmtt) 4.[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl]- quinolinc-7-carboxylic acid (2-amino-l,1-dimethyl-ethyl)-amide, uuuuuuu) 7-(l-Methyl-pyrrolidin-3-ylmcthoxy)-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, vvvvvv) 7-(l -Mcthyl-pipcridin-4-ylmethoxy)-4-(2-pyridin-2-yl-5,6- dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinolinc, wwwwwww) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyiTolo{ 1,2- b]pyrazol-3-yl]-quino!ine-7-carboxy)icacid(2-dimethylamino-l,I-ditncthyl-eihyl)-amidc, xxxxxxx) 4-(6-Pyridin-2-yl-2,3-dihydro-pyrazolo[5,l-b]oxazol-7-y))- quinoline, yyyyyyy) 3-[4-(2-Pyridin-2-yI-5,6-dihydro-4H-pyrrolo( 1,2-b]pyrazol-3-yl)- quinolin-7-yl]-oxazolidin-2-one, zzzzzzz) I -[4-(2-Pyridin-2-yl -5,6-dihydro-4H-pyiTolo[ 1,2b]pyrazol-3-yI)- quinolin-7-y|]-imidazolidin-2-ortc, aaaaaaaa) 4-(2-Pyriclin-2-yl-5,6-dihydro-4H-pyrrolo[l,2-b)pyrazol-3-yl)-7- (pyridin-4-ylmethoxy)-quinolin«, bbbbbbbb) 4-(2-Pyridin-2.yl-516-dihydro-4H-pyTTolo[U-b]pyrazol-3-yl)-7-(3- pyridin-3-yl-propoxy)-quinolinc, cccccccc) 7-(4,5-Dihydro-1 H-imidazol-2-yl)-4-(2-pyridin-2-yl-5,6-dihydro- 4H-pyrrolo[ 1,2-b]pyrazol-3-yl)-quinoline, dddddddd) 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b}pyrazol- 3-yl]-quino)inc-7-carboxylic acid (2-dimcthylamino-1-methyl-cthyl)-amide, eeeeeece) 4-[2-(6-Methyl-pyridin-2-yl)5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol- 3-yl]-quinoline-7-carboxylic acid amide, fffTfffl) 4-(2-Pyridin-2-yl 5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol-3-yl)(- quinolinc-7-carboxylic acid (3-dimeThylamino-propyl)-amidc, gggggggg) 4-[2-(6-Mcthyl-pyridIn-2-yl)-5,6-dihydro-4H-pyrrolo[ 1,2-b]pyrazol- 3-yI]-quinolinc-7-carboxylicacid(2-dimethylamino-cthyl)-mcthyl-amidc, hhhhhhhh) N,N-Dimethyl-3-{4-[2 pyrTolo[ 1,2-b3pyrazol-3-yl]-quinolin-7-yl}-acrylafnidc, iiiiiiii) 7-BenzyIoxy-4-[2-(6-methyI-pyridin-2-yl)~5,6-dihydro-4H-pyrrolo{ 1,2- b]pyrazo!-3-yI]-quinoline, jiijjlijj) N,N-Dimethyl-3-{4-[2-(6-methy1-pyridin-2-yI)-5,6-dihydro-4H- pyrrolo( 1,2-b]pyTazol-3-yl3-quinolin-7-yl}-acryIamidc, and the pharmaceutically acceptable salts and esters. 7. A pharmaceutical formulatian comprising a compound as claimed in claim 1 to 6, or the pharmaceutically accep :abie salt ester thereof with a pharmaceutically acceptable diluent or carrier. 8. A compound as claimed in claim 1, wherein compound is 3-bromo-2-(6-methyl- pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[l,2-b]pyrrazole. Novel pyrrazole compounds and their use as pharmaceutical agents, in particular their use as TGF-beta signal transduction inhibitors. The disclosed invention relates to compounds of the structure (I) wherein (1) is a four, five, or six membered saturated ring and X is C, O or S. |
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1359-KOLNP-2003-(04-01-2013)-FORM-27.pdf
1359-KOLNP-2003-(05-01-2012)-FORM-27.pdf
1359-KOLNP-2003-CORRESPONDENCE.pdf
1359-kolnp-2003-granted-abstract.pdf
1359-kolnp-2003-granted-assignment.pdf
1359-kolnp-2003-granted-claims.pdf
1359-kolnp-2003-granted-correspondence.pdf
1359-kolnp-2003-granted-description (complete).pdf
1359-kolnp-2003-granted-examination report.pdf
1359-kolnp-2003-granted-form 1.pdf
1359-kolnp-2003-granted-form 13.pdf
1359-kolnp-2003-granted-form 18.pdf
1359-kolnp-2003-granted-form 2.pdf
1359-kolnp-2003-granted-form 26.pdf
1359-kolnp-2003-granted-form 3.pdf
1359-kolnp-2003-granted-form 5.pdf
1359-kolnp-2003-granted-gpa.pdf
1359-kolnp-2003-granted-reply to examination report.pdf
1359-kolnp-2003-granted-specification.pdf
| Patent Number | 228787 | |||||||||||||||||||||||||||||||||||||||||||||
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| Indian Patent Application Number | 1359/KOLNP/2003 | |||||||||||||||||||||||||||||||||||||||||||||
| PG Journal Number | 07/2009 | |||||||||||||||||||||||||||||||||||||||||||||
| Publication Date | 13-Feb-2009 | |||||||||||||||||||||||||||||||||||||||||||||
| Grant Date | 11-Feb-2009 | |||||||||||||||||||||||||||||||||||||||||||||
| Date of Filing | 22-Oct-2003 | |||||||||||||||||||||||||||||||||||||||||||||
| Name of Patentee | ELI LILLY AND COMPANY | |||||||||||||||||||||||||||||||||||||||||||||
| Applicant Address | LILLY CORPORATE CENTER, CITY OF INDIANAPOLIS, STATE OF INDIANA | |||||||||||||||||||||||||||||||||||||||||||||
Inventors:
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| PCT International Classification Number | C07D 487/04 | |||||||||||||||||||||||||||||||||||||||||||||
| PCT International Application Number | PCT/US2002/11884 | |||||||||||||||||||||||||||||||||||||||||||||
| PCT International Filing date | 2002-05-13 | |||||||||||||||||||||||||||||||||||||||||||||
PCT Conventions:
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