Title of Invention

INDAZOLE DERIVATIVES AS CRF ANTAGONISTS

Abstract

This invention relates to compounds which are generally CRF-1 receptor antagonists and which are represented by Formula I or Formula II: wherein R<3> is optionally substituted aryl or heteroaryl, R<1> and R<2> are as defined in the specification; or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof. The invention further relates to processes for preparing such compounds, to pharmaceutical compositions containing such compounds, and to methods for their use as therapeutic agents.

Full Text

Indazole derivatives as CRF antagonists This invention relates indazole derivatives of formula I and II with CRF activity, and associated pharmaceutical compositions, and methods for use as therapeutic agents. Corticotropin releasing factor (CRF) or hormone (CRH) is one of several neurohormones synthesized by specific hypothalamic nuclei in the brain where it activates the transcription of the proopiomelanocortin (POMC) gene resulting in release of adrenocorticotropic hormone (ACTH) and beta-endorphin from anterior pituitary cells (Vale etal, Science 213, 1394-1397 (1981)). The fundamental role of CRF is to prepare the organism for an appropriate response to various stressors such as physical trauma, insults of the immune system and social interactions. CRF also has CNS effects by acting at higher centers in the brain, particularly cortical regions where there is a widespread distribution of CRF neurons. CRF is believed to be a key intermediary in communication between the immune, central nervous, endocrine and cardiovascular systems (Sapolsky et al, Science 238, 522-524 (1987)). The role played by CRF in integrating the response of the immune system to physiological, psychological and immunological stressors has been described in the art, e.g. J.E. Blalock, Physiological Reviews 69,1 (1989) and J.E. Morley, Life Sci. 41, 527 (1987). CRF antagonists are effective in the treatment of a wide range of stress-related illnesses, mood disorders such as depression, major depressive disorder, single episode depression, recurrent depression, child abuse induced depression, postpartum depression, dysthemia, bipolar disorder and cyclothymia; chronic fatigue syndrome; eating disorders such as obesity, anorexia and bulimia nervosa; generalized anxiety disorder; panic disorder; phobias; obsessive-compulsive disorder; post-traumatic stress disorder; pain perception such as fibromyalgia; headache; stress-induced gastrointestinal dysfunction such as irritable bowel syndrome (IBS), colonic hypersensitivity or spastic colon; hemorrhagic stress; ulcers; stress-induced psychotic episodes; inflammatory disorders such as rheumatoid arthritis and osteoarthritis; asthma; psoriasis; allergies; premature birth; hypertension; congestive heart failure; sleep disorders; neurodegenerative diseases such as Alzheimer's :ase, senile dementia, Parkinson's disease and Huntington's disease; head or spinal cord ima; ischemic neuronal damage; excitotoxic neuronal damage; epilepsy; stroke; psycho-[al dwarfism; chemical dependencies and addictions; drug and alcohol withdrawal sym-ms; stress-induced immune dysfunctions; immune suppression and stress-induced in-ions; cardiovascular or heart related diseases; fertility problems; and /or human im-riodeficiency virus infections. Accordingly clinical data suggests that CRF receptor ant-nists may represent novel antidepressants and/or anxiolytic drugs that may be useful in treatment of the neuropsychiatry disorders manifesting hypersecretion of CRR In view of the above, efficacious and specific antagonists of CRF are desired as potentially valuable therapeutic agents for the treatment of psychiatric disorders and neurological diseases. It is thus desirable to discover new CRF antagonists. WO 02/16348 describes indazole derivatives which are inhibitors of vascular endothelial growth factor. WO 01/58869 discloses indazole derivatives which are cannabinoid receptor modulators. This invention relates to compounds comprising Formula I wherein: R1 is -NRaRb, -CRcRdRe, C02Ra, or -C(0)NRaRb; or R1 is hydrogen, cycloalkenyl, aryl, or heteroaryl, where each aryl or heteroaryl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl, Q-6 alkoxy, Q-6 alkylthio, Q-6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, -C(0)NRaRb', and -NRaRb', where Ra' and Rb' are each independently selected from the group consisting of hydrogen, Q_9 alkyl, and C1-9 alkylcarbonyl; R2 is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl~Q_3 alkyl, C1-6 alkylcarbonyl, C1-6 alkylsulfonyl, aryl, or arylalkyl, wherein said aryl or arylalkyl is optionally substituted with one or more substituents independently selected from Ci_6 alkyl, haloalkyl, C1-6 alkoxy, and halogen; R3 is aryl or heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, Q-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NRa Rb , where Ra and Rb are each indepen-dently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkyl-carbonyl; Ra and R (i) taken independently are each selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, Q-e alkylthioalkyl, carboxyalkyl, acyl, C3_6 cycloalkyl, C3-6 cycloalkyl-Ci_3 alkyl, di-C3_6cycloalkyl-Ci_3 alkyl, Q^heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and Ci_3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cyclo-alkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkyl-sulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or (ii) taken together, along with the nitrogen atom to which they are attached, are a heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, pipe-ridine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, amino-sulfonyl, aikylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from Q.6 alkyl, haloalkyl, C^e alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piper-azinyl group; Rc is hydrogen, hydroxy, Q-6 alkoxy, or —NR R ; Rd and Re are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, Ci_6 alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3_6 cycloaIkyl-Ci_3 alkyl, di-C3_6 cycloalkyl-Q^ alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Ci_3alkyl, and C1-3 alkyl substituted with both a C3_6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Ci-6 alkyl, haloalkyl, Ci_6 alkoxy, amino, alkylamino, dialkylamino, and halogen; or Rc and Rd are taken together to form a divalent group selected from Q-6 alkylidenyl, C1-6 heteroalkylidenyl, C3.6 cycloalkylidenyl, C3-6 cycloalkyl-alkylidenyl, C3H5cycloaIkyl-Ci_3 alkyl-alkylidenyl, C3_6heterocyclylidenyl, Q^ heterocydyl-Ci-3 alkylidenyl, C3_6hetero-cyclylalkyl-Ci.3 alkylidenyl, aryl-Ci-3 alkylidenyl, aryl-Q.3 alkyl-alkylidenyl, heteroaryl-C1-3 alkylidenyl, and heteroarylalkyl-Ci_3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from Q-6 alkyl, haloalkyl, Q-g alkoxy, amino, alkylamino, dialkylamino, and halogen; or Rd and Re are taken together with the carbon to which they are attached to form a cyclo-alkyl or heterocyclyl ring; Mt 1111 Rd andRD (i) are each independently selected from the group consisting of hydrogen, C\. 9 alkyl, hydroxyalkyl, C\^ alkoxyalkyl, C1-6 alkylthioalkyl, carboxyalkyl, acyl, C3_6 cyclo-alkyl, C3_6 cycloalkyl-Q_3 alkyl, di-C3-6 cycloalkyl-Ci.3 alkyl, C1-6 heteroalkyl, amino-alkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, aryl-alkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Ci_3 alkyl, and C1.3 alkyl substituted with both a C$-t cycloalkyl and a phenyl group, wherein each of said cyclo-alkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-e alkyl, haloalkyl, Ci_6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkyl-sulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or (ii) are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-isoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminpsulfonylarnino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from Q-6 alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group; In another embodiment there is provided a compound of formula I wherein R3 is a 2,4-di-substituted or 2,4,6-trisubstituted phenyl, and the substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6alkoxy, Q-e alkylthio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, II "Llf IT TM cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9alkyl, and C1-9 alkylcarbonyl and R1 and R2 are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are each independently selected from the group consisting of C1-6 alkyl, Q-6 alkoxy, Q_ In another embodiment there is provided a compound of formula I wherein R is hydro-gen, Q-6 alkyl, or Q-e alkylcarbonyl and R" is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are each independently selected from the group consisting of C1-6alkyl, C1-6 alkoxy, Q-e alkylthio, halogen, haloalkyl, cyano, alkylamino, dialkylamino, and nitro and R1 is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRCR Re; Rc is hydroxy; R is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halo-gen, haloalkyl, cyano, nitro, and-NR R , where R andR are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl, and R , Rd and Re are as defined herein above. In another embodiment there is provided a compound of formula I wherein R1 is -CRcRdRe; Rc is hydroxy and R and Re are each independently selected from the group consisting of hydrogen, C1-9 alkyl, Q-e alkoxyalkyl, C3-6 cycloalkyi, C3-6 cycloa!kyl-Ci_3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q_e alkyl, haloalkyl, C1-6 alkoxy, and halogen; RD is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of C1-6 alkyl, Q-g alkoxy, C1-6 alkylthio, Ci-6 alkylsulfonyl, aminosulfonyl, monoalkylamino- ii 1^11 «i sulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R K" and R are each independently selected from the group consisting of hydrogen, C1-9alkyl, and C1-9 alkylcarbonyl, and R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRCR Re; Rc is hydroxy and R and Re are each independently selected from the group consisting of C1-9 alkyl, Q_e alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen; R3 is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of C1-6 alkyl, Q.6 alkoxy, C1-6 alkylthio, Q-e alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and II -Lit Q« LM -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl; and, R is as defined herein above. In another embodiment there is provided a compound of formula I wherein R is -CRcRdRe; Rc is hydroxy and Rd and Re are each independently selected from the group consisting of C1-9 alkyl, Q-6 alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen; R is C1-6 alkyl; and R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are each independently selected from the group consisting of Q-6 alkyl, Q-6 alkoxy, halo- II 'LI! It VII gen, haloalkyl, cyano, and -NR R , where R and R are each independently selected from the group consisting of hydrogen and C1-9 alkyl. In another embodiment there is provided a compound of formula I wherein R is -CRcRdRe; Rc is hydroxy and Rd and Re are taken together to form a cycloalkyl or hetero-cyclyl group; R is C1-6 alkyl; and R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are each independently selected from the group consisting of Q-e It V» II LII alkyl, C1-6 alkoxy, halogen, haloalkyl, cyano, and -NR R , where R and R are each independently selected from the group consisting of hydrogen and C1-9alkyL In another embodiment there is provided a compound of formula I, wherein R is -CRcRdRe; Re is selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, C1-6 cycloalkyl, C1-6 cycloalkyl-Q-3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q-e alkoxy, and halogen; Rc and Rd are taken together to form a divalent group selected from Q-6 alkyl-idenyl, Q-eheteroalkylidenyl, Q-6 cycloalkylidenyl, C1-6 cycloalkyl-alkyHdenyl, C1-6cyclo- alkyl~Q_3 alkyl-alkylidenyl, C1-6heterocyclylidenyl, C1-6heterocyclyl-Q_3 alkylidenyl, C3.6 heterocyclylalkyl-Q_3 alkylidenyl, aryl~Q_3 alkylidenyl, aryl-Q_3 alkyl-alkylidenyl, hetero-aryl-Q_3 alkylidenyl, and heteroarylalkyl-Q_3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen; R is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of Ci-e alkyl, C1-6 alkoxy, Q.6 alkylthio, C1-6 alkylsulf-onyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, it -Lti it vn cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl, and R1 is as defined hereinabove. In another embodiment there is provided a compound of formula I, wherein R1 is -CRCR Re; Re is selected from the group consisting of Ci_9 alkyl, C1-6 alkoxyalkyl, C1-6 cyclo-alkyl, C3_6 cycloalkyl-Ci_3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen; Rc and R are taken together to form a divalent group selected from Q-g alkyl-idenyl, C3_6 qrcloalkyl-alkylidenyl, aiyl-Q-3 alkylidenyl, and heteroaryl-Q_3 alkylidenyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, Q„6 alkoxy, amino, alkyl-amino, dialkylamino, and halogen; R" is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of Q-e alkyl, C1-6 alkoxy, Q-6 alkylthio, C1-6aikylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulf-onyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9alkyl, and C1-9aikylcarbonyl, and R is as defined hereinabove. In another embodiment there is provided a compound of formula I, wherein R is -CRcRdRe; Re is selected from the group consisting of C1-9alkyl, C1-6 alkoxyalkyl, and heteroaryl, where the heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q-6 alkoxy, and halogen; Rc and Rd are taken together to form a divalent group selected from C1-6 alkylidenyl, C3..6 cycloalkyl-alkylidenyl, aryl-Q-3 alkylidenyl, and heteroaryl-Q_3 alkylidenyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from Q-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkyl-amino, dialkylamino, and halogen; R3 is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of Q_e alkyl, Q,6 alkoxy, C1-6 alkylthio, Q-6 alkyistdfonyl, aminosulfonyl, monoalkyiaminosulfonyl, dialkylaminosulf- » -i» »i Lit onyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, Q,9 alkyl, and C1-9 alkylcarbonyl, and R is as defined hereinabove. In another embodiment there is provided a compound of formula I, wherein R1 is CRcRdRe; Rc is hydrogen; and R2, R3, Rd and Re are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is CRCR Re; Rc is hydrogen; R and Re are each independently selected from the group consisting of C1-9 alkyl, Q„6 alkoxyalkyl, Q_e cycloalkyl, C3-6 cycloalkyl-Q-3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-ealkyl, haloalkyl, C1-6alkoxy, and halogen and R , R are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is CRCR Re; Rc is hydrogen; R and Re are each independently selected from the group consisting of C1-9 alkyl, Q_e alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q-e alkoxy, and halogen; R is Q-6 alkyl; and R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are independently selected from the group consisting of C1-6 alkyl, Q-6 alkoxy, halogen, haloalkyl, cyano, and -NRa RD , where Ra and RD are each independently selected from the group consisting of hydrogen and C1-9 alkyl. In another embodiment there is provided a compound of formula I wherein R1 is -NRaR ; -C(0)NRaRb; or -CRcRdRe, where RC is -NR^R*"; Rd and Re are each independently ry « V til selected from the group consisting of hydrogen and C1-9 alkyl; and R , R , Ra, R , R , and 1 Ml R are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -NRaR ; -C(0)NRaRb; or -CRcRdRe, where RC is -NRan,Rb"'; Rd and Re are each independently selected from the group consisting of hydrogen and C1-9 alkyl; R , R , R , and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, Q. 6 alkoxyaUcyl, C3.6 cycloalkyl-Ci-3 alkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, Q_e alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyi, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubsti-tuted or disubstituted with alkyl; and, R and R are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -NRaRb; -C(0)NRaRb; or -CRcRdRe, where RC is -NRaV"; Rd and Re are each independently selected from the group consisting of hydrogen and Q„9 alkyl; Ra and R , or, Ra and Rb are taken together with the nitrogen to which they are attached form an heterocyclyl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydro-pyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimi-dine, hexahydropyrimidine, pyrazoHdine, piperazine, morpholine, and imidazoline, where each of said rings is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy, oxo, alkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, and aminocarbonylamino, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group; and, R and R are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -NRaRb; Ra is selected from the group consisting of hydrogen, C1-9 alkyl, and C1-6 alkoxyalkyl; and R is selected from the group consisting of C1-9alkyl, hydroxyalkyl,C1-6cycloalkyl-Q-3 alkyl, C1-6alkoxyalkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected-from the group consisting of C1-6alkyl, haloalkyl, C1-6 alkoxy, amino, alkyl-amino, diallcylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; R3 is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of C1-6alkyl, C1-6 alkoxy, C1-6alkylthio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9alkylcarbonyl; and R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is -NRaR ; Ra is selected from the group consisting of hydrogen, C1-9 alkyl, and C1-6alkoxyalkyl; and Rb is selected from the group consisting of C1-9 alkyl, C3-6 cycloalkyl-Q_3 alkyl, hydroxyalkyl, C1-6alkoxyalkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents indepen- dently selected from the group consisting of Q^ alkyl, haloalkyl, d-e alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; R is C1-6 alkyl; and R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are independently selected from the group consisting of C1-6alkyl, C1-6 alkoxy, halogen, haloalkyl, cyano, and -NR R , where R and R are each independently selected from the group consisting of hydrogen and C1-9 alkyl. In another embodiment there is provided a compound of formula I wherein R1 is -CR3RaRe; Rc is -NRa R° ; Ra and Re are each independently selected from the group con- in sisting of hydrogen and Q^alkyl; R is selected from the group consisting of hydrogen, ■» iw C1-9 alkyl, and C1-6alkoxyalkyl; R is selected from the group consisting of C1.9 alkyl, C3-6 cycloalkyl-Ci-3 alkyl, hydroxyalkyl, C1-6alkoxyalkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; R is a di- or tri-substituted phenyl which substituents are each independendy selected from the group consisting of Q„6 alkyl, C1-6alkoxy, C\^ alkylthio, Q-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, di-alkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9alkyl, and C1-9alkylcarbonyl; and R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRcRdRe; Rc is -NRa Rb ; Rd and Re are each independently selected from the group con- in sisting of hydrogen and C1-9 alkyl; R is selected from the group consisting of hydrogen, C1-9alkyl, and C1-6alkoxyalkyl; R is selected from the group consisting of Cj_9 alkyl, C3-6 cycloalkyl-Ci-3 alkyl,hydroxyalkyl, C1-6 alkoxyalkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; R is Ci-e alkyl; and R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are independently selected from the group consisting of Cx_6 alkyl, Q-6 alkoxy, halogen, haloalkyl, cyano, and 11 1" II \t> -NRa RD, where Ra and RD are each independently selected from the group consisting of hydrogen and C1-9alkyl. In another embodiment there is provided a compound of formula I wherein R1 is aryl or heteroaryl, where said aryl or heteroaryl is optionally substituted with one or more sub-stituents independently selected from C1-6 alkyl, C1-6 alkoxy, Q^ alkylthio, C1-6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, and -NRaR , where Ra and Rb are each independently selected from the group consisting of hydrogen, Q_$ alkyl, and C1-9alkylcarbonyl; R3 is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of C1-6 alkyl, Q-6 alkoxy, Q~6 alkylthio, Q-6 alkylsulfonyl, aminosulf-onyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NRa RD, where Ra and RD are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1.9 alkylcarbonyl; and R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is aryl or heteroaryl and said aryl or heteroaryl is optionally substituted with one or more substituents independently selected from Q-e alkyl, C1-6 alkoxy, halogen, haloalkyl, cyano, and -NRaRD, whereRa andRD are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9alkylcarbonyl R is a di- or tri-substituted phenyl which substituents are each independently selected from the group consisting of Q,6 alkyl, C1-6 alkoxy, C1-6 alkylthio, Q-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkyl-aminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9alkyl, and C1-9 alkyl-carbonyl; and R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, Q-6 alkylthio, Q-e alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and It Lit _H 1_M -NR R , where R andR are each independently selected from the group consisting of hydrogen, C1-9alkyl, and C1-9 alkylcarbonyl; and, R and R"* axe as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is a 2,4- disubstituted, 2,6-disubstituted, or 2,4,6-trisubstituted pyridin-3-yl, said the substituents are each independently selected from the group consisting of Q„g alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulf- it in » vn onyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each indepen- dently selected from the group consisting of hydrogen, C1.9 alkyl, and C1-9alkylcarbonyl; and, R1 and Rz are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is a 2,4-di-substituted, 2,6-disubstituted, or 2,4,6-trisubstituted pyridin-3-yl, and said substituents are each independently selected from the group consisting of C1-6 alkyl, C^ alkoxy, halo-gen, haloalkyl, alkylamino, and dialkylamino; and, R and R are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is a 2,4-di-substituted, 2,6-disubstituted, or 2,4,6-trisubstituted pyridin-3-yl, and said substituents are each independently selected from the group consisting of C1-6 alkyl, Q-s alkoxy, halo-gen, haloalkyl, alkylamino, and dialkylamino; R is hydrogen, C1-6 alkyl, or C1-6 alkylcarbonyl; and R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRCR Re; Rc is hydroxy; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Q-e alkyl, C1-6 alkoxy, Q-g alkyl-thio, Ci-6alkylsulfonyl, aminosulfonyl, monoallcylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and ~NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9alkyl, and C1-9 alkylcarbonyl; and, R , Rd and Re are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRCR Re; Rc is hydroxy; R and Re are each independently selected from the group consisting of hydrogen, Ci„9 alkyl, Q-6 alkoxyalkyl, C^-e cycloalkyl, C^e cycloalkyl-Ci-3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independentiy selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen; R3 is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, Q-6 alkylthio, C1-6alkylsulfonyl, aminosulfonyl, mono-alkylaminosulfonyl, dialkylarninosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , vhere Ra" and Rb" are each independently selected from the group consisting of hydrogen, 3i_9 alkyl, and Qu9 alkylcarbonyl; and, R is as defined hereinabove. Ln another embodiment there is provided a compound of formula I wherein R is -CRcRdRe;-Rc is hydroxy; Rd and Re are each independently selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-e alkyl, haloalkyl, Q-6 alkoxy, and halogen; R3 is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Q,6 alkyl, C1-6 alkoxy, Q-e alkylthio, C1-6alkylsulfonyl, aminosulf-onyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NRa RD, where Ra and RD are each independently selected from the group consisting of hydrogen, C1.9 alkyl, and C1-9 alkyicarbonyl; and R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRCR Re; Rc is hydroxy; R and Re are each independently selected from the group consisting of C1-9 alkyl, Q-e alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or hetero-aryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Cue alkoxy, and halogen; R is C1-6alkyl; and R is a 2,4-disubstituted, 2,6-disubstituted, or 2,4,6-trisubstituted pyridin-3-yl, and the substituents are each independently selected from the group consisting of C1-6 alkyl, Q-e tl UI It » (1 alkoxy, halogen, haloalkyl, and -NR R , where R and R are each independently selected from the group consisting of hydrogen and C1-9 alkyl. In another embodiment there is provided a compound of formula I wherein R1 is -CRCR Re; Rc is hydroxy; wherein R and Re are taken together to form a cycloalkyl or heterocyclyl group; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Ci_e alkyl, Q-6 alkoxy, C1-6alkylthio, Q-ealkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halo- ri tn 11 in gen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkyicarbonyl; and, R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRcRdRe; Re is selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, C1-6 cycloalkyl, C3_6 cycloalkyl-Ci-3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen; Rc and R are taken together to form a divalent group selected from Q-e alkyl-idenyl, Q-eheteroalkylidenyl, C1-6cycloalkylidenyl, Q-6 cycloalkyl-alkylidenyl, C3_6cyclo-alkyl-Q-3 alkyl-alkylidenyl, Q-eheterocyclylidenyl, C3.6heterocyclyl-Ci-3alkylidenyl, C3_6 heterocyclylalkyl-Q-3 alkyHdenyl, aryl-Ci_3 alkylidenyl, aryl-Q.3 alkyl-alkylidenyl, hetero-aryl-Ci.3 alkylidenyl, and heteroarylalkyl-Q_3 alkyHdenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, Q_$ alkoxy, amino, alkylamino, dialkylamino, and halogen; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Ci-e alkyl, C1-6alkoxy, C1-6alkylthio, C1-6alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, Cj_9 alkyi, and C1-9 alkylcarbonyl; and, R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is ~CRCR Re; Re is selected from the group consisting of C1.9 alkyi, C\^ alkoxyalkyl? C3.S cyclo-alkyl, Cs~6 cycloalkyl-Q_3 alkyi, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyi, haloalkyl, Q-6 alkoxy, and halogen; Rc and R are taken together to form a divalent group selected from Q.-6 alkyl-idenyl, C3_6 cycloalkyl-alkylidenyl, Cs-eheterocyclylidenyl, aryl-Ci.3 alkylidenyl, andhetero-aiyl-Q .3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from Q-e alkyi, halo-alkyi, Q .6 alkoxy, amino, alkylamino, dialkylamino, and halogen; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of C1-6 alkyi, Ci„6 alkoxy, Q-g alkylthio, Q.g alkylsulfonyl, aminosulfonyl, mono-alkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where Ra and R are each independently selected from the group consisting of hydrogen, C1-9 alkyi, and C1.9 alkylcarbonyl; and, and R are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is -CRCR Re; Re is selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, and heteroaryl, where the heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of Ci_e alkyl, haloalkyl, Cue alkoxy, and halogen; and Rc and R are taken together to form a divalent group selected from C1-6 alkylidenyl, C3.6 cycloalkyl-alkylidenyl, C3-6heterocydyl-Ci_3 alkylidenyl, aryl-Q-3 alkylidenyl, and heteroaryl-Q-3 alkylidenyl, wherein each of said aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from Q^ alkyl, C1-6alkoxy, amino, alkylamino, and dialkylamino; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of C1-6alkyl, Q-6 alkoxy, C1-6 alkylthio, Ci-6 alkylsulfonyl, aminosulfonyl, monoalkyl-aminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where Ra andRD are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and Ci.9 alkylcarbonyl; and, and R" are as defined hereinabove. In another embodiment there is provided a compound of formula I, wherein R1 is -CRCR Re; Rc is hydrogen; R3 is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Gi_e alkyl, C1-6 alkoxy, Q_e alkyl-thio, Ci-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl,-halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9alkylcarbonyl; and, R2, Rd and Re are as defined hereinabove. In another embodiment there is provided a compound of formula I, wherein R1 is -CRcRdRe; Rc is hydrogen; Rd and Re are each independently selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, Q-ecycloalkyl, Q-6cycloalkyl-Q_3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl3 where each of said aryl or heterqaryl groups is optionally substituted with one or more substituents independently selected from the group consist-ing of Q-6 alkyl, haloalkyl, Q_$ alkoxy, and halogen; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Q-6 alkyl, Q-6 alkoxy, Q_e alkylfhio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NRa Rb, where Ra and R are each independently selected from the group consisting of hydrogen, Ci_9 alkyl, and C1-9 alkylcarbonyl; and, R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRCR Re; Rc is hydrogen; R and Re are each independently selected from the group consisting of C1-9 alkyl, Q_e alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of .Q_e alkyl, haloalkyl, Q_e alkoxy, and halogen; R is Q_ 6 alkyl; and R is a 2,4-disubstituted, 2,6-disubstituted, or 2,4,6-txisubstituted pyridin-3-yl, and the substituents are independently selected from the group consisting of C1-6 alkyl, Q-6 alkoxy, halogen, haloalkyl, and -NR R , where R and R are each independently selected from the group consisting of hydrogen and C1-9alkyl. In another embodiment there is provided a compound of formula I wherein R is -NRaR ; -C(0)NRaRb; or -CRcRdRe, where RC is -NR^R*"; Rd and Re are each independently selected from the group consisting of hydrogen and Ci_9 alkyl; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Q-6 alkyl, d-e alkoxy, Q-6 alkylfhio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylamino- IT -f II II sulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and Rb" are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl; and, R , Ra, R , Ra , and R are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -NRaRb; -C(0)NRaRb; or -CRcRdRe, where RC is -NR^R^; Rd and Re are each independently selected from the group consisting of hydrogen and C1-9alkyl; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6alkoxy, Q-e alkylthio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylamino-sulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NRa Rb , where Ra r 11 andRD are each independently selected from the group consisting of hydrogen, Ci_9 alkyl, V _«• I'll and Ci_9 alkylcarbonyl; R , R , R , and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6alkoxyalkyl, C3_6cycloalkyl-Ci_3 alkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkyl-amino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; and, R2 is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is -NRaR ; -C(0)NRaRb; or -CRcRdRe, where RC is -NRa'"Rb'"; Rd and Re are each independently selected from the group consisting of hydrogen and C1-9alkyl; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, Q~6 alkylthio, C^e alkylsulfonyl, aminosulfonyl, monoalkylamino-sulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, '- ■L 1« V1I1 and Ci_9 alkylcarbonyl; R and R , or R and R , are taken together with the nitrogen to which they are attached form an heterocyclyl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, and imidazoline, where each of said rings is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy, oxo, alkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, and aminocarbonylamino, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group; and, R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is'-NRaR ; Ra is selected from the group consisting of hydrogen, C1-9alkyl, and C1-6 alkoxyalkyl; R is selected from the group consisting of C1-9alkyl, C3.6 cycloalkyl-Q.3 alkyl, hydroxyalkyl, d-e alkoxyalkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Q-e alkyl, C1-6 alkoxy, C1-6alkylthio, C1-6 alkylsulf-onyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , \\rhere R and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9alkylcarbonyl; and, R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -NRaR ; Ra is selected from the group consisting of hydrogen, C1-9alkyl, and C1-6 alkoxyalkyl; R is selected from the group consisting of C1-9 alkyl, C1-6 cycloalkyl-Q-3 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, heteroq^clylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q_e alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; R is C1-6 alkyl; and R is a 2,4-disubstituted, 2,6-disubstituted, or 2,4,6-trisubstituted pyridin-3-yl, and the substituents are independently selected from the group consisting of Q-6 alkyl, Q-6 alkoxy, halogen, haloalkyl, and -NR R , where R andR are each independently selected from the group consisting of hydrogen and C1-9 alkyl. In another embodiment there is provided a compound of formula I wherein R is -CRcRdRe; Rc is NR^R5"; Rd and Re are each independently selected from the group con-sisting of hydrogen and C1-9 alkyl; R is selected from the group consisting of hydrogen, I HI C1-9alkyl, and Q_e alkoxyalkyl; R is selected from the group consisting of C1-9alkyl, C3.6 cycloalkyl-Q-3 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, heterocyclylalkyl, arylalkyl, and hetero-arylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkyl-sulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; R3 is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of C1-6alkyl, Q-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NRaRb, where Ra" and Rb" are each independently selected from the group consisting of hydrogen, Q,9 alkyl, and C1-9alkylcarbonyl; and, and R are as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R1 is -CRcRQRe; Rc is NRa RD ; Ra and Re are each independently selected from the group consist-ing of hydrogen and C1-9alkyl; R is selected from the group consisting of hydrogen, C1-9 alkyl, and C1-6 alkoxyalkyl; R is selected from the group consisting of C1-9 alkyl, C1-6 cyclo-alkyl-Q_3 alkyl, hydroxyalkyl, Q-6 alkoxyalkyl, heterocyclylalkyl, arylalkyl, and heteroaryl-alkyl, wherein each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulf-onyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally mono-substituted or disubstituted with alkyl; R is Q.g alkyl; and R is a 2,4-disubstituted, 2,6-disubstituted, or 2,4,6-trisubstituted pyridin-3-yl, and the substituents are independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, halogen, haloalkyl, and rt IM 11 -i n -NRa RD , where Ra and RD are each independently selected from the group consisting of hydrogen and C1-9alkyl. In another embodiment there is provided a compound of formula I wherein R is aryl or heteroaryl, where said aryl or heteroaryl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, Q_e alkylthio, Q_ I II I LI onyl, halogen, haloalkyl, cyano, nitro, and —NR R , where R and R are each indepen-dently selected from the group consisting of hydrogen, C1-9alkyl, and C1-9alkylcarbonyl; R is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of Q-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, Q^ alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NRa RD, where Ra and RD are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9alkylcarbonyl; and, R is as defined hereinabove. In another embodiment there is provided a compound of formula I wherein R is aryl or heteroaryl, where said aryl or heteroaryl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, Q-6 alkoxy, halogen, haloalkyl, cyano, and -NRaRb', where Ra' and Rv are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9alkylcarbonyl; R3 is a di- or tri-substituted pyridinyl, and said substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, Q.$ alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkyl-aminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each ted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piper- azinyl group; or, individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof; with the proviso that if R1 is -CRcRdRe, R2 is hydrogen or alkyl, R3 is a 5- or 6-membered heteroaryl ring, and (i) Rc is hydrogen and one of R and Re is hydrogen or alkyl, then the other of R and Re is other than hydrogen or alkyl if the number of carbon atoms in R and Re together are zero to three; or, (ii) Rcis hydrogen and one of R and Re is hydrogen or alkyl, then the other of R and Re is other than alkoxy, alkoxyalkyl, heterocyclyl, heterocyclylalkyl, or heteroalkyl; or, . -ttr -itir rn r HI HI (iii) Rcis NRa Rb and one of Ra and Rb is hydrogen or Cx.3 alkyl, then the other of Ra and R is other than hydrogen or Q_3 alkyl. In one embodiment the present invention provides a compound of formula I wherein R is optionally substituted phenyl. In another embodiment the present invention provides a compound of formula I wherein R is a di- or tri-substituted phenyl. In still another em-bodiment the present invention provides a compound of formula I wherein R is a 2,4-di-substituted or 2,4,6-trisubstituted phenyl. In still another embodiment the present inven-tion provides a compound of formula I wherein R is a 2,4-disubstituted or 2,4,6-trisubsti-tuted phenyl, and the substituents are each independently selected from the group consisting of Ci-6 alkyl, Que alkoxy, C1-6 alkylthio, halogen, haloalkyl, cyano, alkylamino, dialkyl- amino, and nitro. '•• In still another embodiment the present invention provides a compound of formula I wherein R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, C1-6 alkyl-thio, halogen, haloalkyl, cyano, alkylamino, dialkylamino, and nitro, and R is hydrogen, Ci-6 alkyl, or Q_e alkylcarbonyl. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and Rz is -CRcRdRe and Rc is hydroxy. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is -CRcRdRe wherein Rc is hydroxy, and Rd and Re are each independently selected from the group consisting of hydrogen, C1-9 alkyl, Q-e alkoxyalkyl, C3.6 cycloalkyl, Q_e cycloalkyl-Q-3 alkyl, aryl, arylalkyl, heteroaryl, and hetero-arylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloallcyl, Q-6 alkoxy, and halogen. In another embodiment the present invention provides a compound of formula I wherein R~ is a di- or tri-substituted phenyl and R is -CRCR Re wherein Rc is hydroxy and R and Re are each independently selected from the group consisting of C1-9 alkyl, Q-6 alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q„$ alkyl, haloalkyl, C1-6 alkoxy, and halogen. In another embodiment the present invention provides a compound of formula I wherein R1 is -CRCR Re wherein Rc is hydroxy and R and Re are each independently selected from the group consisting of C1-9alkyl, C1-6 alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q_e alkyl, haloalkyl, C1-6 alkoxy, and halogen, R is Q-6 alkyl; and R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are each independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, halogen, haloalkyl, cyano, and -NR R , where R and R are each independently selected from the group consisting of hydrogen and Ci_9 alkyl. In another embodiment the present invention provides a compound of formula I wherein R is a di- ortri-substituted phenyl and R is -CRCR Re wherein Rc is hydroxy and R and Re are taken together to form a cycloalkyl or heterocyclyl group. In another embodiment the present invention provides a compound of formula I wherein R~ is a di- or tri-substituted phenyl and R1 is -CRCR Re wherein Re is selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, Q-6 cycloalkyl, C1-6 cydoaIkyl-Q..3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-g alkyl, haloalkyl, C1-6 alkoxy, and halogen; and Rc and R are taken together to form a divalent group selected from Q-6 alkylidenyl, Q.eheteroalkylidenyl, C1-6 cycloalkylidenyl, C3.6 cycloalkyl-alkylidenyl, C1-6 qrcloalkyl-Q_3 alkyl-alkylidenyl, C3_6 heterocyclylidenyl, Q-6heterocyclyl-Q-3 alkylidenyl, C1-6heteroqrclylalkyl-Q.3 alkylidenyl, aryl-Ci-3 alkylidenyl, aryl-Q-3 alkyl-alkylidenyl, heteroaryl-Ci.3 alkylidenyl, and heteroaryl-alkyl-Q-3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted. In another embodiment the present invention provides a compound of formula I wherein R is a di- or tri-substituted phenyl and R is -CRCR Re wherein Re is selected from the group consisting of C1-9 alkyl, Cj_6 alkoxyalkyl, C1-6 cycloalkyl, C1-6 cycloalkyl-Q_3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independentiy selected from the group consisting of Q-6 alkyl, haloalkyl, Q-s alkoxy, and halogen; and Rc and Rd are taken together to form a divalent group selected from Q-6 alkylidenyl, C3_6 cydoalkyl-alkylidenyl, aryl-Ci_3 alkylidenyl, and heteroaryl-Ci_3 alkylidenyl, wherein each of said aryl or heteroaryl groups is optionally substituted. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is -CRCR Re wherein Re is selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, and heteroaryl, where the heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen; and Rc and R are taken together to form a divalent group selected from C1-6 alkylidenyl, C1-6 cycloaBcyl-alkylidenyl, C3_6heterocyclyl-Ci-3 alkylidenyl, aryl-Q-3 alkylidenyl, and heteroaryl-Q-3 alkylidenyl, wherein each of said aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from Q-s alkyl, Q-6 alkoxy, amino, alkylamino, and dialkylamino. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is -CRCR Re wherein Rc is hydrogen. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is -CRCR Re wherein Rc is hydrogen and R and Re are each independently selected from the group consisting of C1-9alkyl, C1-6 alkoxyalkyl, C3-6 cycloalkyl, C3.6 cycloaIkyl-Q-3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, Q-6 alkoxy, and halogen. In another embodiment the present invention provides a compound of formula I wherein R1 is -CRcRdRe wherein Rc is hydrogen and R and Re are each independently selected from the group consisting of C1-9 alkyl, Q_e alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q.g alkoxy, and halogen; R2 is Q-6 alkyl; and R3 is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substi- tuents are independently selected from the group consisting of d_6 alkyl, Q-g alkoxy, halo- it -lit ir yit gen, haloalkyl, cyano, and -NR R , where R andR are each independently selected from the group consisting of hydrogen and C1-9 alkyl. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is -NRaRb; -C(0)NRaRb; or -CRcRdRe, wherein tit 1 »1 J a Rc is -NRa RD , and RQ and Re are each independently selected from the group consisting of hydrogen and Ci_9 alkyl. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is -NRaRb; -C(0)NRaRb; or -CRcRdRe, wherein Rc is -NRa RD , and RQ and Re are each independentiy selected from the group consisting of hydrogen and C1-9 alkyl, wherein R , R , R , and R are each independently selected from the group consisting of hydrogen, Ci_9 alkyl, hydroxyalkyl, Q.g alkoxyalkyl, C^e cycloalkyl-Ci_3 alkyl, heterocyclylalkyl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is -NRaRb; -C(0)NRaRb; or -CRcRdRe, wherein 111 1 W J Rc is -NRa RD , and RQ and Re are each independently selected from the group consisting of hydrogen and C1-9 alkyl, wherein R and R , or R and R , are taken together with the nitrogen to which they are attached form an heterocyclyl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydro-quinoline, 1,2,3,4-tetrahydroisoquinoHne, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, and imidazoline, where each of said rings is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy, oxo, alkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, and aminocarbonylamino, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. In another embodiment the present invention provides a compound of formula I wherein a 1 -i R is a di- or tri-substituted phenyl and R is -NRaR wherein Ra is selected from the group consisting of hydrogen, QI9 alkyl, and Ci_e alkoxyalkyl; and R is selected from the group consisting of C1-9 alkyl, hydroxyalkyl, Ci_e alkoxyalkyl, C3-6 cycloalkyl-Q.3 alkyl, hetero-cyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted. In another embodiment the present invention provides a compound of formula I wherein R1 is -NRaR wherein Ra is selected from the group consisting of hydrogen, C1.9 alkyl, and C1-6alkoxyalkyl; and R is selected from the group consisting of C1-9 alkyl, hydroxyalkyl, C1-6alkoxyalkyl, C1-6cycloalkyl-Q_3 alkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted; R2 is C1-6 alkyl; and R3 is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are independently selected from the group consisting of Q^ alkyl, Q_e alkoxy, halogen, haloalkyl, tt 'Ltl II Lit cyano, and -NRa RD , wherein Ra and RD are each independently selected from the group consisting of hydrogen and Q .9 alkyl. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is -CRcRdRe wherein Rc is -NR'V; Rd and Re in are each independently selected from the group consisting of hydrogen and C1.9 alkyl; R is selected from the group consisting of hydrogen, C1-9alkyl, and C1-6 alkoxyalkyl; and, R is selected from the group consisting of C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 q^cloalkyl-Ci-s alkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted. In another embodiment the present invention provides a compound of formula I wherein R1 is -CRcRdRe wherein Rc is -NR^R*"; Rd and Re are each independently selected from the group consisting of hydrogen and C1-9alkyl; R is selected from the group consisting of " * Lttt hydrogen, C1-9alkyl, and C^6 alkoxyalkyl; and, R is selected from the group consisting of C1-9 alkyl, hydroxyalkyl, Q.g alkoxyalkyl, C1-6 cycloalkyl-Q_3 alkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally sub-stituted; R is C1-6 alkyl; and R is a 2,4-disubstituted or 2,4,6-trisubstituted phenyl, and the substituents are independently selected from the group consisting of Q_e alkyl, C1-6alkoxy, 11 Lit » L« halogen, haloalkyl, cyano, and -NR R , where R and R are each independently selected from the group consisting of hydrogen and C1-9 alkyl. In another embodiment the present invention provides a compound of formula I wherein R is a di- or tri-substituted phenyl and R is aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more substituents independently selected from Q-6 alkyl, Q_e alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, and -NRaRb', where Ra' and Rb' are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9alkylcarbonyl. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted phenyl and R1 is aryl or heteroaryl, wherein said aryl or hetero- aryl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl, C1-6alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, and -NRaRD, whereRa andRD are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1.9 alkylcarbonyl, where said aryl or heteroaryl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, 1 LI I "LI halogen, haloalkyl, cyano, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl. In one embodiment the present invention provides a compound of formula I wherein R is an optionally substituted pyridinyl. In another embodiment the present invention pro-vides a compound of formula I wherein R is a di- or tri-substituted pyridinyl. In another embodiment the present invention provides a compound of formula I wherein R is a di- or tri-substituted pyridinyl and R is -CRCR Re wherein Rc is hydroxy. In another embodiment the present invention provides a compound of formula I wherein R is a di- or tri-substituted pyridinyl and R is -CRCR Re wherein Rc is hydroxy and R and Re are each independently selected from the group consisting of hydrogen, C1-9alkyl, Q_e alkoxyalkyl, C1-6 cycloalkyl, C3-6 cycloalkyl-Q_3 alkyl, aryl, arylalkyl, heteroaryl, and hetero-arylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6alkoxy, and halogen. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted pyridinyl and R1 is -CRCR Re wherein Rc is hydroxy and R and Re are each independently selected from the group consisting of C1-9alkyl, C1-6 alkoxyalkyl, aryl, and heteroaryl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, Q-6 alkoxy, and halogen. In another embodiment the present invention provides a compound of formula I wherein R3 is a di- or tri-substituted pyridinyl and R1 is -CRcRdRe wherein Rc is hydroxy and Rd and Re are taken together to form a cycloalkyl or heterocyclyl group. In one embodiment the present invention provides a compound of formula I wherein R is an optionally substituted pyridinyl and R1 is -CRcRdRe wherein Re is selected from the group consisting of C1-9 alkyl, Q-6 alkoxyalkyl, C3_6 cycloalkyl, C3-6 cycloalkyl-Q_3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Cu6 alkyl, haloalkyl, C1-6alkoxy, and halogen; and Rc and Rd are taken together to form a divalent group selected from Ci-6 alkylidenyl, Q.sheteroalkylidenyl, C3_6 cycloalkylidenyl, C3-6 cycloalkyl-alkylidenyl, C3_6cycloaIkyl-Ci.3 alkyl-alkylidenyl, C3.6 heterocyclylidenyl, C3-6heterocyclyl-Ci-3 alkylidenyl> C3_6heterocyclylaIkyl-Ci_3 alkylidenyl, aryl-Ci-3 alkylidenyl, aryl-Q_3 alkyl-alkylidenyl, heteroaryl-Q-3 alkylidenyl, and heteroaryl-aIkyl-Q-3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted. In one embodiment the present invention provides a compound of formula I wherein R3 is an optionally substituted pyridinyl and R1 is -CRCR Re wherein Re is selected from the group consisting of Qu9 alkyl, Q-6 alkoxyalkyl, C3.6 cycloalkyl, C$.6 cycloalkyl-Ci-3 alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl> where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C^s alkyl, haloalkyl, C1-6 alkoxy, and halogen; and Rc and Rd are taken together to form a divalent group selected from Q-e alkylidenyl, C3_6 cycloalkyl-alkyHdenyl, aryl-Ci_3 alkylidenyl, and heteroaryl-Ci_3 alkylidenyl. In one embodiment the present invention provides a compound of formula I wherein R is an optionally substituted pyridinyl and R1 is -CRcRdRe wherein Re is selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, and heteroaryl, where the heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of Q-ealkyl, haloalkyl, Gi.6 alkoxy, and halogen; and Rc and R are taken together to form a divalent group selected from Q-g alkylidenyl, C3-6 cycloalkyl-alkylidenyl, C3_6 heterocyclyI-Ci.3 alkylidenyl, aryl-Q-3 alkylidenyl, and heteroaryl-Q-3 alkylidenyl, wherein each of said aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from C^e alkyl, C1-6 alkoxy, amino, alkylamino, and dialkylamino. In one embodiment the present invention provides a compound of formula I wherein R is an optionally substituted pyridinyl and R1 is -CRCR Re wherein Rc is hydrogen. In one embodiment the present invention provides a compound of formula I wherem R is an optionally substituted pyridinyl and R1 is -CRcRdRe wherein Rc is hydrogen and R and Re are each independently selected from the group consisting of QJ9 alkyl, Q_s alkoxyalkyl, C3.6 cycloalkyl, C3.6 cydosJkyl-Ci.s alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where each of said aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-e alkyl, haloalkyl, d-e alkoxy, and halogen. In one embodiment the present invention provides a compound of formula I wherein R3 is an optionally substituted pyridinyl and R1 is -NRaRb; -C(0)NRaRb; or -CRcRdRe, wherein in v tn j Rc is -NRa RD ; and Ra and Re are each independently selected from the group consisting of hydrogen and C^alkyl. In one embodiment the present invention provides a compound of formula I wherein R3 is an optionally substituted pyridinyl and R1 is -NRaRb; -C(0)NRaRb; or -CRcRdRe, wherein Rc is -NRa RD ; and Ra and Re are each independently selected from the group consisting of -i in t in hydrogen and Q^alkyl, wherein R , R , R , and R are each independently selected from the group consisting of hydrogen, C1.9 alkyl, hydroxyalkyl, C1-6alkoxyalkyl, C3_6 cycloalkyl- Q-3 alkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl. In one embodiment the present invention provides a compound of formula I wherein R is an optionally substituted pyridinyl and R1 is -NRaRb; -C(0)NRaRb; or -CRcRdRe, wherein Rc is -NRa RD ; and RQ and Re are each independently selected from the group consisting of hydrogen and Ci^alkyl, R and R , or R and R , are taken together with the nitrogen to which they are attached form an heterocyclyl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoHne, tetrahydropyrimidine, hexahydropyrimidine, pyrazohdine, piperazine, morpholine, and imidazoline, where each of said rings is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy, oxo, alkyl, aminoallcyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, and aminocarbonylamino, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. In one embodiment the present invention provides a compound of formula I wherein R is an optionally substituted pyridinyl and R1 is -NRaR wherein Ra is selected from the group consisting of hydrogen, C1-9alkyl, and Q-e alkoxyalkyl; and R is selected from the group consisting of C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C^6 cycloalkyl-Q-3 alkyl, hetero-cyclylalkyl, arylalkyl, and heteroarylalkyl. In one embodiment the present invention provides a compound of formula I wherein R is an optionally substituted pyridinyl and R1 is -CRcRdRe wherein Rc is -NR^R*"; Rd and Re are each independently selected from the group consisting of hydrogen and C1-9 alkyl; R ■LUt is selected from the group consisting of hydrogen, Ci_9 alkyl, and Q-6 alkoxyalkyl; and R is selected from the group consisting of C1.9 alkyl, hydroxyalkyl, C1-6alkoxyalkyl, C3.6 cycloalkyl-Ci-3 alkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said aryl or heteroaryl groups is optionally substituted. In one embodiment the present invention provides a compound of formula I wherein R3 is an optionally substituted pyridinyl and R1 is aryl or heteroaryl wherein said aryl or heteroaryl is optionally substituted. In one embodiment the present invention provides a compound of formula I wherein R3 is an optionally substituted pyridinyl and R1 is aryl or heteroaryl wherein said aryl or heteroaryl is optionally substituted with one or more substituents independently selected from Q-6 alkyl, Q-6 alkoxy, halogen, haloalkyl, cyano, and -NRaRb, where Ra and Rb are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and Q^alkyl-carbonyl. In one embodiment the present invention provides a compound of formula I wherein R1 is -NRaRb, -CRcRdRe, C02Ra, or -C(0)NRaRb. In another embodiment the present invention provides a compound of formula I wherein R1 is -NRaRb> wherein Ra and R are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6alkoxyalkyl, C1-6 alkyltbioalkyl, carboxyalkyl, acyl, C3-6 cyclo-alkyl, C3-6cycloa^M"Ci-3 alkyl, di-C3_6 cycloalkylCi-3 alkyl, Q^heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and Ci_3 alkyl substituted with both a C3_6"cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfon-yloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or Ra and Rb are taken together with the nitrogen to which they are attached form an hetero-cyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, l>2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-isoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from Ci-6alkyl, haloalkyl, C1-6alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. In still another embodiment the present invention provides a compound of formula I wherein R1 is -NRaR , wherein Ra and Rb are each independently selected from the group consisting of hydrogen, Ci_9 alkyl, hydroxyalkyl, Q-ealkoxyalkyl, Q-6 alkylthioalkyl, carboxyalkyl, acyl, C3_6 cyclo-alkyl, C3-6 cycloalkyl-Q_3 alkyl, di-C3_6cydoalkylCi_3 alkyl, Q-eheteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and Q-3 alkyl substituted with both a C3_6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q^ alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfon-yloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl. In still another embodiment the present invention provides a compound of formula I wherein R1 is -NRaRb, wherein Ra and Rb are each independently selected from the group consisting of C1-9 alkyl, C1-6 alkoxyalkyl, C3-6 cycloalkyl-Q-3 alkyl, arylalkyl, heteroarylalkyl, wherein each of said cycloalkyl, aryl or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkoxy and cyano. In still another embodiment the present invention provides a compound of formula I wherein R1 is -NRaR , wherein Ra and Rb are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinohne, 1,2,3,4-tetrahydxo-isoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6alkyl, haloalkyl, C1-6alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. In still another embodiment the present invention provides a compound of formula I wherein R1 is -NRaR , wherein Ra and R are taken together with the nitrogen to which they are attached form morpholine. In another embodiment the present invention provides a compound of formula I wherein R1 is -C(0)NRaRb, wherein Ra and Rb are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, Q-e alkoxyalkyl, Q.s alkylthioalkyl, carboxyalkyl, acyl, C3.6 cyclo-alkyl, C3.6 cycloalkyl-Q.3 alkyl, di-C3_6cycloalkylCi-3 alkyl, Ci_6heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, Cs_8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and Q_3 alkyl substituted with both a C3-6cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6alkoxy, amino, alkylainino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfon-yloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or RaandRb are taken together with the nitrogen to which they are attached form an hetero-cyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-isoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6 alkyl, haloalkyl, Ci-e alkoxy, amino,-alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. In still another embodiment the present invention provides a compound of formula I wherein R1 is -C(0)NRaRb, wherein Ra and Rb are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6alkoxyalkyl, C1-6 alkylthio alkyl, carboxyalkyl, acyl, C3-6 cycloalkyl, C3-6 cycloaftyl-Ci_3 alkyl, di-C3-6 cydoalkylQ.3 alkyl, C1-6heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and Ci_3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulf-onyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl. In still another embodiment the present invention provides a compound of formula I wherein R1 is -C(0)NRaRb, wherein Ra and R are each independently selected from the group consisting of C1-9 alkyl, Q^ alkoxyalkyl and C3-6 cycloalkyl-Q-3 alkyl. In still another embodiment the present invention provides a compound of formula I wherein R1 is -C(0)NRaRb, wherein Ra and Rb are taken together with the nitrogen to which they are attached form an hetero-cyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-isoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acyl-amino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosxalfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6alkyl, haloalkyl, Ci_e alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. In still another embodiment the present invention provides a compound of formula I wherein R1 is -C(0)NRaRb, wherein Ra and Rb are taken together with the nitrogen to which they are attached form morpholine. In another embodiment the present invention provides a compound of formula I wherein R1 is -CRcRdRe wherein _ in -Lirr R is hydrogen, hydroxy, C1-6 alkoxy, or -NR R ; RaandRe are each independently selected from the group consisting of hydrogen, Q.g alkyl, hydroxyalkyl, C1-6alkoxyalkyl, C^e alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3_6cycloalkyl-Ci_3 alkyl, di-C3-6 cycloalkyl-Q-3 alkyl, aryi, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Q^alkyl, and Gu$ alkyl substituted with both a C$s cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, halo-alkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen; or Rc and Rd are taken together to form a divalent group selected from C1-6alkylidenyl, C1-6heteroalkylidenyl, C3.6 cycloalkyUdenyl, C3-6 cycloalkyl-alkylidenyl, C3-6 cycloalkyl-Ci-3 alkyl-alkylidenyl, C3_6heterocyclylidenyl, C3.6 heterocyclyl-Ci.3 alkylidenyl, C3_6hetero-cyclylalkyl-Ci.3 alkylidenyl, aryl-Q_3 alkylidenyl, aryl-Ci-3 alkyl-alkylidenyl, heteroaryl-C1.3 alkyhdenyl, and heteroarylalkyl-Ci_3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from Ci_s alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen; or Rd and Re are taken together with the carbon to which they are attached to form a cycloalkyl or heterocyclyl ring; tn 1 «r Ra andRD are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, Q-e alkoxyalkyl, Q-6 alkylthioalkyl, carboxyalkyl, acyl, C3_6 cycloalkyl, C3-6 cycloalkyl-Ci-3 alkyl, di-C3-e cycloaIkyl-Ci_3 alkyl, Q-6 heteroalkyl, amino-alkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Ci_3 alkyl, and Q-3 alkyl substituted with both a C3.6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C\-e alkyl, haloalkyl, C1-6alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosub-stituted or disubstituted with alkyl; or Ra and Rb taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-isoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acyl- amino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. In still another embodiment the present invention provides a compound of formula I wherein R1 is -CRcRdRe wherein Rc is -NRa Rb ; R and Re are hydrogen; R and R taken together with the nitrogen to which they are attached form an hetero-cyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydxoquinoline, 1,2,3,4-tetrahydroiso-quinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from Ci>6 alkyl, haloalkyl, Q-e alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. In still another embodiment the present invention provides a compound of formula I wherein R1 is -CRcRdRe wherein Re is hydrogen, Ci_9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3.6 cycloalkyl-Q-3 alkyl, di-C3_6 cyclo-alkyl-Ci_3 alkyl? aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Ci_ 3alkyl, and Q-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, Q-e alkoxy, amino, alkylamino, dialkylamino, and halogen; and Rc and Rd are taken together to form a divalent group selected from Que alkylidenyl, C1-6 heteroalkylidenyl, C3-6cycloalkylidenyl, C3-6 cycloalkyl-alkylidenyl, C3.6cycloalkyl-Ci-3 alkyl-alkylidenyl, C3.6heterocyclylidenyl, C3_6heterocydyl-Ci_3alkylidenyl, C3_6hetero-cyclylalkyl-Ci-3 alkylidenyl, aryl-Q_3 alkylidenyl, aryl-Q_3 alkyl-alkylidenyl, heteroaryl-Q_3 alkylidenyl, and heteroarylalkyl-Ci_3 alkyiidenyl> wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from Q-e alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, and halogen. In still another embodiment the present invention provides a compound of formula I wherein R1 is -CRcRdRe wherein Rc is -NRa Rb ; Rd and R£ are each independently selected from the group consisting of hydrogen, Ci_9 alkyl, hydroxyalkyl, Q^alkoxyalkyl, C1-6alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3_6 cycloalkyl-Ci-3 alkyl, di-C3_6 cycloalkyl-Ci_3 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Q^alkyl, and Q.3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6alkyl, haloalkyl, C1-6alkoxy, amino, alkylamino, dialkylamino, and halogen; or •It VIM Ra andRD are each independently selected from the group consisting of hydrogen, C1-9alkyl, hydroxyalkyl, Q-ealkoxyalkyl, Q-e alkylthioalkyl, carboxyalkyl, acyl, C3.6 cycloalkyl, C3_6 qrcloalkyl-Q_3 alkyl, di-C3_6 cycloalkyl-Gi_3 alkyl, Cueheteroalkyl, amino-alkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, aryl-alkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Ci-3 alkyl, and Q_3 alkyl substituted with both a C3_e cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkyl-sulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl. In still another embodiment the present invention provides a compound of formula I wherein R1 is -CRcRdRe or -C(0)NRaRb wherein RC is -NRa Rb ; wherein Ra and Rb taken together with the nitrogen to which they are attached form morpholine; R and Re are hydrogen; andRa and Rb taken together with the nitrogen to which they are attached form morpholine. In one embodiment the present invention provides a compound of formula I wherein R" is C1-6alkyl. In one embodiment the present invention provides a compound of formula I wherein R3 is aryl or heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of Q-e allcyl, Ci-g alkoxy and halogen. In one embodiment the present invention provides a compound of formula I selected from . 7-(2,4-dicHoro~phenyl)-2-methyl-3-( l-propyl-but-l-enyl)-2H-indazole hydrochloride, 2-methyl-3-(l-propyl-but-l-enyl)-7-(24>6-trimethyl-phenyl)-2H~indazolehydrocWoride, 3-(3-metho:^-1-met±Lo:!qra 2H-indazole hydrochloride, [7-(2,4-dicMoro-phenyl)-2-methyl-2H-m [2-methyl-7-(2>436-trimethyl-phenyl)~2H-indazol-3-yl]-dipropyl-aminehydrocM (2-methoxy-ethyl)-[2-methyl-7-(2>4,6-trimethyl-phenyl)-2H-indazol-3-yl]-propyl-ami^^ hydrochloride, ethyl-(2-methoxy-etlLyl)-[2-me&^^ hydrochloride, cyclopropylmetliyl-[2-methy^ trifluoroacetic acid salt, furan-2-ylmetliyl-[2-metliyl-7-(2,4,6-trimetiiyl-phenyl)-2H-indazol-3-yl]-p trifluoroacetic acid salt, [2-methyl-7-(2,4,6-trimethyl-phenyl)-2H^ amine trifluoro-acetic acid salt, Bis-(2-metlioxy-elliyl^^^ hydrochloride, 2-methyl-7-(2,4>6-trimethyl-^^ propyl-amide, cyclopropylmetliyl-[2-metiyl-7-(2^ amine hydrochloride, [7-(6-methoxy-2-methyl-pyri^ fluoroacetate, 7-(2,4-dicMoro-phenyl)-2-metfayl-2if-indazole-3-carboxyhcacidcyclopropylmethyl- propyl-amide, 7-(2,4-dicWoro-phenyl)-2-metbyl-2H-m^ amide trifluoroacetate, 7-(2,4-dichloro-phenyl)-2-methyl-2H-indazole-3-carboxylic acid diethylamide trifluoroacetate, [7-(2,4-dicUoro-phenyl)-2-methyl-2H-indazol-3-yl]-morpholin-4-yl-methanone, 7-(2>4-dicMoro-phenyl)-2-ethyl-2H-indazole-3-carboxylicacidcyclopropyhnethyl-propyl-amide trifluoroacetate, 7-(2>4-dicUoro-phenyl)-2-methyl-3-((E)-l-propyl-but-l-enyl)-2H-indazoleJ [7-(4-methoxy-2-methyl-phenyl)-2-meth^^ chloride, (2-methoxy-ethyl) - [ 7- (4-methoxy-2-methyl-phenyl) -2-methyl-2H-indazol-3-yl] -propyl-amine hydrochloride, cyclopropylmethyl-(2-methoxy-ethyl)-[7-(4-methoxy-2-meth.yl-phenyl)-2-m indazol-3-yl]-amine hydrochloride, 7-(2,4-dimethoxy-phenyl)-2-methyl-3-(l-propyl-but-l-enyl)-2H-indazole hydrochloride, cyclopropylmethyl-[7-(2,4-dichloro-phenyl)-2-m hydrochloride, cyclopropylmethyl-[7-(2,4-dicUoro-phenyl)-2-methyl-2H-indazol-3-ylmethyl]-propyl-amine trifluoroacetate, [7-(2,4-dimethoxy-phenyl)-2-methyl-2H-indazol-3-yl]-dipropyl-aminehydrocUoride, 4-({[2-methyl-7-(2,4,6-trimethyl-phenyl)-2H-indazol-3-yl]-propyl-amino}-methyl)-benzonitrile trifluoroacetate, benzyl- [2-methyl-7-(2,4,6-trimethyl-phenyl)-2H-indazol-3-yl] -propyl-amine trifluoroacetate, 7-(6-methoxy-2-methyl-pyridin-3-yl)-2-methyl-3-((E)-l-propyl-but-l-enyl)-2H-indazole hydrochloride, dimethyl-{4-methyl-5-[2-methyl-3-(^^ 2-yl}-amine trifluoroacetate, [2-methyl-7- (2,4,6-trimethyl-phenyl) -2H-indazol-3-yl] -propyl-thiazol-2-ylmethyl-amine trifluoroacetate, (3,4-dimethoxy-benz}i)-[2-methyl-7-(2,4,6-trimethyl-phenyl)-2H-indazol-3-yl] -propylamine trifluoroacetate and 7-(2,4-dichloro-phenyl)-2-methyl-3-morpholin-4-ylmethyl-2H-indazole. In another embodiment the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of at least one compound of formula I or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof; in admixture with at least one pharmaceutically acceptable carrier. In another embodiment the present invention provides a method for treating a subject having a disease state that is alleviated by treatment with a CKF receptor antagonist, which comprises administering to such a subject a therapeutically effective amount of a com- pound of formula I or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutical^ acceptable salts thereof. In another embodiment the present invention provides a method for treating a subject having a disease state that is alleviated by treatment with a CRF receptor antagonist which comprises administering to such a subject a therapeutically effective amount of a compound of formula I or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof, wherein the disease state is selected from the group consisting of phobias, stress-related illnesses, mood disorders, eating disorders, generalized anxiety disorders, stress-induced gastrointestinal dysfunctions, neurodegenerative diseases, and neuropsychiatric disorders. Unless otherwise stated, the following terms used in this Application, including the specification and claims, have the definitions given below. The phrase "a" or "an" entity as used herein refers to one or more of that entity; e.g., a compound refers to one or more compounds or at least one compound. As such, the terms "a" (or "an"), "one or more", and "at least one" can be used interchangeably herein. The phrase "as defined hereinabove" refers to the first definition provided in the Detailed Description of the Invention. The term "alkyl" as used herein means a monovalent unbranched or branched saturated hydrocarbon radical, consisting solely of carbon and hydrogen atoms, having from one to ten carbon atoms inclusive, unless otherwise indicated. Examples of alkyl radicals include, but are not limited to, methyl, ethyl, propyl, iso-propyl, zso-butyl, sec-butyl, tert-butyl, pentyl, n-hexyl, and the like. The term "lower alkyl" lower alkyl refers to alkyl group having from one to six carbon atoms. The term "alkylene" as used herein means a divalent unbranched or branched saturated hydrocarbon radical consisting solely of carbon and hydrogen atoms, having from one to ten carbon atoms inclusive, unless otherwise indicated. Examples of alkylene radicals include, but are not limited to, methylene, ethylene, propylene, 2-methylethylene, 3-methyl-propylene, 2-ethylethylene, pentylene, hexylene, and the like. The term "alkoxy" as used herein means a radical -OR, wherein R is a lower alkyl radical as defined herein. Examples of alkoxy radicals include, but are not limited to, mefhoxy, eth-oxy, isopropoxy, and the like. The term "cycloalkyl" as used herein means a monovalent saturated carbocyclic radical consisting of one or more rings, and consisting solely of carbon and hydrogen atoms, having from three to eight carbon atoms inclusive, unless otherwise indicated. Examples of cycloalkyl radicals include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl, and the like. The term "substituted cycloalkyl" as used herein means the cycloalkyl as defined herein, including one to three substituents, such as hydroxy, cyano, lower alkyl, lower alkoxy, thio-alkyl, halo, haloalkyl, hydroxyalkyl, nitro, alkoxycarbonyl, amino, alkylamino, dialkyl-amino, aminocarbonyl, carbonylamino, aminosulfonyl, and sulfonylamino. Examples of cycloalkyl radicals include, but are not limited to, 3-ethylcyclobutyl, 4-hydroxycyclohexyl 3-chlorcyclopentyl and the like. The term "cycloalkylalkyl" as used herein means a radical -RR", wherein Rr is an alkylene radical, and R" is a cycloalkyl or substituted cycloalkyl radical as defined herein. Examples of cycloalkylalkyl radicals include, but are not limited to, cyclopropylmethyl, cyclohexyl-methyl, cyclopentylethyl, and the like. The term "cycloalkenyl" as used herein means a monovalent unsaturated carbocyclic radical consisting of one or more rings, and consisting solely of carbon and hydrogen atoms, having from one to ten carbon atoms inclusive, unless otherwise indicated. Examples of cycloalkenyl radicals include, but are not limited to, cyclobuten-1-yl, cyclopenten-1-yl and the like. The term "substituted cycloalkenylyl" as used herein means the cycloalkenyl as defined herein, including one to three substituents, such as hydroxy, cyano, lower alkyl, lower alkoxy, thioalkyl, halo, haloalkyl, hydroxyalkyl, nitro, alkoxycarbonyl, amino, alkylamino, chalkylamino, aminocarbonyl, carbonylamino, aminosulfonyl, and sulfonylamino, unless otherwise indicated. Examples of substituted cycloalkenyl radicals include, but are not limited to 3-ethylqrclobuten-l-yl, 3-fiuorocyclohepten-l-yl, and the like. The term "halogen" or "halo" as used herein means the radical fluoro, bromo, chloro, or iodo, and combinations thereof The term "haloalkyl" as used herein means a lower alkyl radical as defined herein substituted in any position with one or more halogen atoms as defined herein. Examples of haloalkyl radicals include, but are not limited to, 1,2-difluoropropyl, 1,2-dichloropropyl, tri-fluoromethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and the like. The term "aryF or "aromatic" as used herein means a monocyclic or bicyclic radical of 6 to 12 ring carbon atoms having at least one aromatic ring, with the understanding that the attachment point of the aryl radical will be on an aromatic ring. The aryl radical is optionally substituted independently with one or more substituents selected from alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, acyl, acylamino, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylsulfonyloxy, -S02NR!R" (where R1 and R" are independently hydrogen or alkyl), alkoxy, haloalkoxy, alkoxycarbonyl, carbamoyl, hydroxy, halo, nitro, cyano, thio, methylenedioxy or ethylenedioxy. More specifically the term aryl includes, but is not limited to, phenyl, naphfhyl, tetrahydronaphthyl, 3,4-meth-ylenedioxyphenyl, l,2,3,4-tetrahydroquinolin-7-yl, l,2,3,4-tetrahydro~isoquinoline-7-yl, and the like. The terms "heteroaryl" and "heteroaromatic" as used herein means a monoqrclic or bicyclic radical of 5 to 12 ring atoms having at least one aromatic ring containing one, two, or three ring heteroatoms selected from nitrogen, oxygen, and sulfur, the remaining ring atoms being carbon, with the understanding that the attachment point of the heteroaryl radical will be on an aromatic ring. The heteroaryl ring is optionally substituted independently with one or more substituents selected from alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aqd, acylamino, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulf-onyl> alkylsulfonyloxy, -SOaNR'R" (where R' andR" are independently hydrogen or alkyl), alkoxy, haloalkoxy, alkoxycarbonyl, carbamoyl, hydroxy, halo, nitro, cyano, thio,.methylenedioxy or ethylenedioxy. Examples of heteroaryl moieties include monocyclic aromatic heterocycles having 5 to 6 ring atoms and 1 to 2 heteroatoms include, but is not limited to, including, and includes, but is not limited to, pyridinyl, furanyl, thienyl, thi-azolyl, isothiazolyl, triazolyl, imidazolyl, isoxazolyl, pyrrolyl, pyrazolyl, and pyrimidinyl, and derivatives thereof, and bicyclic aromatic moieties having 9 to 10 ring atoms, including 1 to 3 heteroatoms, and includes, but is not limited to, benzofuranyl, tetrahydrobenzo-furanyl, isobenzofuranyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, indolyl, iso-indolyl, benzoxazolyl, quinolinyl, 5,6,7,8-tetrahydroquinolinyl, isoquinolinyl, 5,6,7,8-tetrahydroisoquinolinyl, benzimidazolyl, benzisoxazolyl, andbenzothienyl, and derivatives thereof. The term "heteroalkyl" sa used herein means an alkyl radical as defined herein wherein one, two, or three hydrogen atoms have been replaced with a substituent independently selected from the group consisting of-ORa, -NRbRc, and -S(0)nRd (where n is an integer from 0 to 2), with the understanding that the point of attachment of the heteroalkyl radical i is through a carbon atom, wherein Ra is hydrogen, acyl, alkyl, q^cloalkyl, or cycloaIkyl-Ci.3 alkyl; and R and Rc are independently selected from the group consisting of hydrogen, acyl, alkyl, cycloalkyl, or cycloalkyl-Ci.3 alkyl; when n is 0, R is hydrogen, alkyl, cycloalkyl, and qrcloalkyl-Ci-3 alkyl and when n is 1 or 2, Rd is alkyl, cycloalkyl, cycloalkyl-Q-3 alkyl, amino, acylamino, monoalkylamino, or dialkylamino. Representative examples include, but are not limited to, 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxy-l-hydroxymethyl-ethyl, 2,3-dihydroxypropyl, 1-hydroxymethylethyl, 3-hydroxybutyl, 2,3-dihydroxybutyl, 2-hydroxy-1-methylpropyl, 2-methoxyethyl, 2-ethoxyethyl, 3-methoxypropyl, 2-aminoethyl? 3-aminopropyl, 2-methylsulfonylethyl, aminosulfonylmethyl, aminosulfonylethyl, amino-sulfonylpropyl, methylaminosulfonyl-methyl, methylaminosulfonylethyl, methylamino-sulfonylpropyl, and the like. The term "heterocyclyl" as used herein means a saturated or unsaturated non-aromatic monocyclic or bicyclic radical of 3 to 10 ring atoms in which one or two ring atoms are heteroatom containing groups selected from NR\ O, or S(0)n (where RT is alkyl, hetero-alkyl, or hydrogen, and n is an integer from 0 to 2), the remaining ring atoms being carbon. The heterocyclyl radical is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, haloalkyl, hydroxyalkyl, hetero-alkyl, and acyl. The term heterocyclyl includes, but is not limited to, tetrahydropyranyl, piperidino, tetrahydropyrimidin-5-yl, tetrahydropyrimidin-1-yl, N-methylpiperidin-3-yl, piperazino, N-methylpyrrolidin-3-yl, 3-pyrroMino, morpholino, thiomorphohno, thio-morpholino-1-oxide, tHomorpholino-l,l-dioxide, pyrrolinyl, imidazohnyl, tetrahydro-quinolin-1-yl and tetrahydroisoquinolin-2-yl, and the like. The term "arylalkyr as used herein means a radical -RTR" where RT is an alkylene radical and R" is an aryl radical as defined herein. Examples of arylalkyl radicals include, but are not limited to, 4-fluorophenylmethyl, 3,4-dichlorophenylethyl> and the like. The term "heteroarylalkyT as used herein means a radical -R'R" where Rf is an alkylene radical and R!,-is a heteroaryl radical as defined herein. Examples of heteroarylalkyl radicals include, but are not limited to, such as 3-pyridinylmethyl, 4-chloropyrimidin-2-yl-methyl, 2-thiophen-2-ylethyl, and the like. The term "heterocyclylalkyl" as used herein means a radical -RTRn where R is an alkylene radical and R" is a heterocyclyl radical as defined Herein. Examples of heterocyclylalkyl radicals include, but are not limited to, tetrahydropyran-2-ylmethyl, 2-piperidinylmethyl, 3-piperidinylmethyl, morpholin-1-ylpropyl, and the like. The term "alkylamino" as used herein means a radical —NRTRM, wherein R' is hydrogen and RT1 is an alkyl radical as defined herein. The term !,dialkylaminoM as used herein means a radical -NR'R", wherein R' and RTI are alkyl radicals as defined herein. Examples of alkyl-amino radicals include, but are not limited to, methylarnino, ethylamino, cyclopropyl-methylamino, dicyclopropylmethylamino, dimethylamino, methylethylamino, diethyl-amino, di(l-methylethyl) amino, and the like. The term "acyT means a formyl radical of the formula -C(0)H, or a carbonyl radical of the formula -C(0)R!, where R is selected from the group consisting of Ci-is alkyl, cyclo-alkyl, cycloalkylalkyl, haloalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, or NR'R", as defined herein, wherein R! and R" are hydrogen of alkyl or R!, R" and the nitrogen to which they are attached are a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group. The term "alkylidenyl" as used herein means a bivalent radical =CRR\ wherein R and R are independently an alkyl radical or hydrogen, as defined herein. Examples of alkylidenyl radicals include, but are not limited to, ethylidenyl, propylidenyl, butylidenyl, and the like. The term "cycloalkyhdenyr as used herein means a bivalent radical =CRR\ wherein R and R1 are taken together with the carbon to which they are attached to form a bivalent cyclo-alkyl radical, as defined herein. Examples of cycloalkylidenyl radicals include, but are not limited to, cyclopentylidenyl, 3-ftuorocyclohexylidenyl, and the like. The term "cycloalkyl-alkylidenyT as used herein means a bivalent radical =CRR', wherein R is an alkyl radical or hydrogen, and R is a cycloalkyl radical, as defined herein. Examples of cycloalkyl-alkylidenyl radicals include, but are not limited to, cyclopropylmethylidenyl, cyclohexylmethylidenyl, 1-cyclopentylethylidenyl, and the like. The term "cycloalkylalkyl-alkylidenyr as used herein means a bivalent radical =CRR\ wherein R is an alkyl radical or hydrogen, and R' is a cycloalkylalkyl radical, as defined herein. Examples of cycloalkylalkyl-alkylidenyl radicals include, but are not limited to, 2-cyclopentylethylidenyl, l-cyclohexylpropyliden-2-yl, and the like. The term "heteroalkylidenyF as used herein means a bivalent radical =CRR\ wherein R is an heteroalkyl radical, an haloalkyl radical, an alkyl radical, or hydrogen, and R' is an heteroalkyl radical or an haloalkyl radical, as defined herein. Examples of heteroalkyl-idenyl radicals include, but are not limited to, 3,3,3-trifluoropropylidenyl, 2-hydroxy-butylidenyl, 3-aminopropylidenyl, and the like. The term "heterocyclylidenyl" as used herein means a bivalent radical =CRRr, wherein R and R! are taken together with the carbon to which they are attached to form a bivalent heterocyclyl radical, as defined herein. Examples of heterocyclylidenyl radicals include, but are not limited to, pyrrolidinyliden-2-yl, tetrahydropyranyliden-4-yl, piperidinyliden-4-yl, and the like. The term "heterocyclyl-alkylidenyT as used herein means a bivalent radical =CRR\ wherein R is an alkyl radical or hydrogen, and R' is a heterocyclyl radical, as defined herein. Examples of heterocyclyl-aBcylidenyl radicals include, but are not limited to, 4-piperidinylmethylidenyl, 4-methyl- 1-piperazinylmefhylidene, and the like. The term "heterocyclylaliyl-alkyhdenyr as used herein means a bivalent radical =CRR', wherein R is an alkyl radical or hydrogen, and R' is a heterocyclylalkyl radical, as defined herein. Examples of heterocyclylalkyl-alkylidenyl radicals include, but are not limited to, 2-(tetrahydropyran-4-yl)ethylidenyl, l-(piperidin-3-yl)propyliden-2-yl, and the like. The term "arylalkylidenyP as used herein means a bivalent radical =CRR', wherein R is an aryl radical, an alkyl radical, or hydrogen, and RT is an aryl radical, as defined herein. Examples of arylalkyhdenyl radicals include, but are not limited to, 4-chlorophenylmethyl-idenyl, 6,7-diniethoxynaphth-2-ylmethylidenyl, and the like. The term "arylalkyl-alkylidenyT as used herein means a bivalent radical =CRR', wherein R is an alkyl radical or hydrogen, and R' is an arylalkyl radical, as defined herein. Examples of arylalkyl-alkylidenyl radicals include, but are not limited to, 2-(4-trifluoromefhyl-phenyl)ethylidenyl, l-(3,4-dichlorophenyl)propyliden-2-yl, and the like. The term "heteroarylalkylidenyF as used herein means a bivalent radical =CRR\ wherein R is an alkyl radical or hydrogen, and R' is a heteroaryl radical, as defined herein. Examples of heteroarylalkylidenyl radicals include, but are not limited to, 3-pyridinyl-methylidenyl, 4-chloro-2-pyrimidinylmethylidenyl, and the like. The term "heteroarylalkyl-alkylidenyl" as used herein means a bivalent radical =CRR\ wherein R is an alkyl radical or hydrogen, and R1 is a heteroarylalkyl radical, as defined herein. Examples of heteroarylalkyl-alkylidenyl radicals include, but are not limited to, 2-(4-1xifluoromethylpyriimdinyl)ethyhdenyl, l-(thiophen-2-yl)propyliden-2-yl, and the like. It is contemplated that the definitions described herein maybe appended to form chemically-relevant combinations, such as "heteroaLkylaryl," "haloalkylheteroaryl," "aryl-alkylheterocyclyl," "alkylcarbonyl," "alkoxyalkyl," and the like. The term "optional" or "optionally" as used herein means that a subsequently described event or circumstance may, but need not, occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, "optional bond" means that the bond may or may not be present, and that the description includes single, double, or triple bonds. "Isomerism" means compounds that have identical molecular formulae but that differ in the nature or the sequence of bonding of their atoms or in the arrangement of their atoms in space. Isomers that differ in the arrangement of their atoms in space are termed "stereoisomers". Stereoisomers that are not mirror images of one another are termed "diastereo-isomers", and stereoisomers that are non-superimposable mirror images are termed "en-antiomers", or sometimes optical isomers. A carbon atom bonded to four nonidentical substituents is termed a "chiral center". "Chiral isomer" means a compound with one chiral center. It has two enantiomeric forms of opposite chirality and may exist either as an individual enantiomer or as a mixture of enantiomers. A mixture containing equal amounts of individual enantiomeric forms of opposite chirality is termed a "racemic mixture". A compound that has more than one chiral center has 2n~* enantiomeric pairs, where n is the number of chiral centers. Compounds with more than one chiral center may exist as either an individual diastereomer or as a mixture of diastereomers, termed a "diastereomeric mixture." When one chiral center is present, a stereoisomer maybe characterized by the absolute configuration ( R or S ) of that chiral center. Absolute configuration refers to the arrangement in space of the substituents attached to the chiral center. The substituents attached to the chiral center under consideration are ranked in accordance with the Sequence Rule of Calm, Ingold and Prelog. (Calm et al. Angew. Chem. Inter. Edit. 1966, 5, 385; errata 511; Cahn et al. Angew. Chem. 1966,78,413; Cahn andlngoldj. Chem. Soc. (London) 1951, 612; Calm et al. Experientia 1956,12, 81; Cahn, J. Chem. Educ. 1964,41,116). "Geometric Isomers" means the diastereomers that owe theifexistence to hindered rotation about double bonds. These configurations are differentiated in their names by the prefixes cis and trans, or Z and E, which indicate that the groups are on the same or opposite side of the double bond in the molecule according to the Cahn-Ingold-Prelog rules. "Atropic isomers53 means the isomers owing their existence to restricted rotation caused by hindrance of rotation of large groups about a central bond. The phrase "substantially pure" as used herein means at least about 90 mole percent of the desired compound, enantiomer or stereoisomer is present compared to other possible configurations. The phrase "pharmaceutically acceptable" as used herein means that which is useful in preparing a pharmaceutical composition that is generally safe, non-toxic, and neither biologically nor otherwise undesirable and includes that which is acceptable for veterinary as well as human pharmaceutical use. The phrase "pharmaceutically acceptable salts" of a compound as used herein means salts that are pharmaceutically acceptable, as defined herein, and that possess the desired pharmacological activity of the parent compound. Such salts include: (i) acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fiimaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, hydroxynaphthoic acid, 2-hydroxyethanesulfonic acid, lactic acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, muconic acid, 2-naphthalenesulfonic acid, propionic acid, salicylic acid, succinic acid, tartaric acid, p-toluenesulfonic acid, trimefhylacetic acid, and the like; or (ii) salts formed when an acidic proton present in the parent compound either is replaced by a metal ion,.e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic or inorganic base. Acceptable organic bases include diethanol-amine, ethanolamine, N-methylglucamine, triethanolamine, tromethamine, and the like-Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate and sodium hydroxide. The preferred pharmaceutically acceptable salts are the salts formed from acetic acid, hydrochloric acid, sulphuric acid, methanesulfonic acid, maleic acid, phosphoric acid, tartaric acid, citric acid, sodium, potassium, calcium, zinc, and magnesium. It should be understood that all references to pharmaceutically acceptable salts include solvent addition forms (solvates) or crystal forms (polymorphs) as defined herein, of the same acid addition salt. The term "crystal forms" or "polymorphs" means crystal structures in which a compound can crystallize in different crystal packing arrangements, all of which have the same elemental composition. Different crystal forms usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability and solubility. Recrystallization solvent, rate of crystallization, storage temperature, and other factors may cause one crystal form to dominate. The term "solvates" as used herein means solvent additions forms that contain either stoichiometric or non-stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate. If the solvent is water the solvate formed is a hydrate, when the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of one or more molecules of water with one of the substances in which the water retains its molecular state as H2O, such combination being able to form one or more hydrate. "Subject" means mammals and non-mammals. Mammals means any member of the Mammalia class including, but not limited to, humans; non-human primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, and swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice, and guinea pigs; and the like. Examples of non-mammals include, but are not limited to, birds, and the like. The term "subject" does not denote a particular age or sex. "Therapeutically effective amount" means an amount of a compound that, when admini-stered to a subject for treating a disease state, is sufficient to effect such treatment for the disease state. The "therapeutically effective amount" will vary depending on the compound, disease state being treated, the severity or the disease treated, the age and relative health of the subject, the route and form of administration, the judgment of the attending medical or veterinary practitioner, and other factors. "Disease state" means any disease, condition, symptom, or indication. "Treating" or "treatment" of a disease state includes: (i) preventing the disease state, Le. causing the clinical symptoms of the disease state not to develop in a subject that maybe exposed to or predisposed to the disease state, but does not yet experience or display symptoms of the disease state; (ii) inhibiting the disease state, i.e., arresting the development of the disease state or its clinical symptoms, or (iii) relieving the disease state, x.e., causing temporary or permanent regression of the disease state or its clinical symptoms. "Mood disorders" or "affective disorders" means psychopathologic conditions in which a pervasive disturbance of mood constitutes the core manifestation. These terms subsume anxiety and related neuroses, especially the depressive form. Examples of "mood disorders" or "affective disorders" include, but are not limited to, depression, major depressive disorder, single episode depression, recurrent depression, child abuse induced depression, postpartum depression, dysthemia, unipolar disorder, bipolar disorder with manifestations of insomnia and eating disorder, dysthymic disorder, double depression, morbid and clinical depression, mania and cyclothymia. In general, the nomenclature used in this Application is based on AUTONOM™ v.4.0, a Beilstein Institute computerized system for the generation of IUPAC systematic nomenclature. The following abbreviations were used throughout the specification: Ac20: Acetic Anhydride; DME: 1,2-dimethoxyethane; DCE: 1,2-dichloroethane; THF: tetrahydrofuran; TEA: txiethylamine; rt: room temperature; Si02: silica gel; EtOH: ethanol; MeOH: methanol; Et20: diethyl ether; EtOAc: ethyl acetate; NaN02: sodium nitrite; NaOAc: sodium acetate; DMSO: dimethyl sulfoxide; pTsOH • H20: p-toluenesulfonic acid mono-hydrate; Pd(PPli3)4(0): tetrakis(triphenyphosphine)palladium(0), BH3-THF: boron hydride-tetrahydrofiiran complex; EDCI: l-(3-dimethylaminopropyl)-3-ethylcarbo-dimide; HOBT: 1-hydroxybenzotriazole hydrate. Examples of Compounds of the Present Invention The following examples and preparations are provided to enable those skilled in the art to more clearly understand and to practice the present invention. They should not be considered as limiting the scope of the invention, but merely as being illustrative and representative thereof. Compound Preparation The compounds of Formulae I and II described herein may be prepared by standard synthetic methods. In particular, certain compounds of Formulae I and II maybe prepared utilizing as an intermediate 7-bromoindazole (3)> the preparation of which is illustrated in Scheme 1. Deprotonation of 3 and N-alkylation of the tautomeric anion with dimethyl sulfate produces a separable mixture of 2-methyl-7-bromoindazole (4) and 1-methyl-7-bromoindazole (18). The R3 (optionally substituted aryl or heteroaryl) substituent can be introduced by standard aryl coupling procedures which are well known in the art. The resulting 7-aryl (or heteroaryl) indazoles, e.g., 4, are readily transformed into the com-. pounds of the present invention as outlined in Schemes 1-3. Similar transformations can be used to convert 18 into the compounds of formula II. SCHEME 1 (a) NaN35 H2S04 (67%); (b) t-BuONO, CuBr2, CH3CN, 60°C (57%); (c) tellurium, NaBH4, EtOH; (d) (f) NaN02,HCl, H20 (it) NaOAc, t-BuSH, EtOH; (e) t-BuO K\ DMSO, RT (98%); (f) (MeO)2S02, NaOH, H20; (g) Pd(PPh3)4(0)? Na^C^, DME3 H20, 2,4-dichlorobenzeneboronic acid, reflux (40%); (h) n-BuLi,THF, -78°; Q) C02; (k) HN03, Ac20; (l) H2,10% Pd/C, MeOH; (m) (j) (PhO)2PON3, TEA, r-Bu-OH; (ii) TFA, CH2C12 Nitration of 4a produces a mixture of regioisomeric nitroindazoles from which the 3-nitroindazole 7a is readily isolated. The nitro substituent can be reduced to the corresponding amine 8a under standard conditions. An alternate route to 8a involves treatment of 4a with n-butyffitium to produce the 3-lithiated heterocycle 11 which is quenched with carbon dioxide to produce carboxylic acid 10a. The amine can be prepared from carboxylic acid 10a utilizing the Curtius rearrangement or a variant thereof (J. March Advanced Organic Chemistry 4th Ed J Wiley & Sons: New York, 1991; pp 1090-1095). Conversion of amine 8a into amide 12a can be achieved by a variety of methodologies well known in the art (J. March Advanced Organic Chemistry 4 Ed J Wiley & Sons: New York, 1991; pp 417-424). Reduction of the amide with borane-THF complex, or other reducing agents, (J. March supra> pp 445-446) affords the secondary amine 13a that can be further transformed to the tertiary amine 15a by reductive animation or via a second acylation and reduction sequence. Alternatively tertiary amines 14a can be prepared directly from 8a by reductive animation. (Scheme 2) The stepwise procedure permits the preparation of tertiary amines with different substituents on the nitrogen atom. The lithiated heteroq^cle 11 (Scheme 3) can be quenched with carbonyl compounds to produce carbinols 5 which, in turn, can be dehydrated to olefins 6 described herein. The dehydration produces a mixture of geometrical isomers. The present invention includes both the pure E and Z isomers and mixtures thereof. The olefins optionally can be further converted to the corresponding alkane 17. SCHEME 3 graphed on Si02-and eluted with 10% acetone in hexane which afforded 1.62g (57%) of 1c as a pale yellow-green liquid. Step 2: 2-Bromo-6-methylaniline (2a) - A mixture of tellurium (21.6 g, 169.4 mmol) and NaBHU (15.0 g, 396 mmol) in 575 mL of absolute EtOH was heated at reflux under an atmosphere of N2 for 1 hr, then allowed to cool to it. A solution of 3-bromo-2-nitro-toluene (lc; 7.32g> 33.8 mmol) in 25 mL EtOH was added all at once and the mixture allowed to stir at room temp for 2 hrs. The reaction mixture was filtered through a CELITE® pad and the filtrate evaporated under reduced pressure. The residue was taken up in Et20 (about 200 mL), washed with brine then dried over MgS04. Evaporation of the solvent afforded 2.66g (42%) of 2a as a dark liquid. Step 3: (2-Bromo-6-methylphenylazo)~t-butylsulfide (2b) - 2-Bromo-6-methylaniline (2a; l-18g, 6.34 mmol) and 3.4 mL 6N HC1 was heated in an oil bath at 60° for 30 min, then cooled to 0°. A solution of NaN02 (481 mg, 6.97 mmol) in 1.5 mL H20 was added drop-wise then stirred in the cold for an additional hr. The reaction mixture was buffered to a pH between 4 and 5 with saturated NaOAc solution, then added all at once to an ice-cold solution of t-butyl mercaptan (0.80 mL, 629 mg, 6.97 mMol) in 14 mL EtOH. The mixture was allowed to warm to rt overnight. The reaction mixture was partitioned between EtOAc (50 mL) and H20 (50 mL). The aqueous layer was re-extracted with EtOAc (50 mL). The combined EtOAc extracts were washed with brine and dried over MgSCU. Evaporation of the solvent afforded 1.46 g (80%) of 2b. Step 4: 7-Bromoindazole (3) - A solution of (2-bromo-6-methylphenylazo)-f-butylsulfide (2b; 880 mg? 3.06 mmol) in 10 mL dry DMSO was added dropwise to a solution of potassium t-butoxide (3.44 g, 30.6 mmol) in 25 mL dry DMSO under Ar. The reaction mixture was stirred at room temp for 2 hr, then poured into 150 g ice and 150 mL 2 N HC1 solution. The mixture was extracted with ether (2 x 150mL). The combined ethereal extracts were washed with brine and dried over MgSO^. Evaporation of the solvent afforded 581 mg (96%) of 3 as a beige solid. Step 5: 7-Bromo~2-methylindazole (4) - A mixture of 7-bromoindazole (3; 576 mg, 2.92 mmol) and NaOH (510 mg, 12.7 mmol) in 15 mL H2O were heated in an oil bath under N2 atmosphere until the solids dissolved and the resulting solution was cooled to 65 °C. Dimethyl sulfate (0.78 mL, 1.03 g, 8.18 mmol) was added and the mixture stirred at 65° for 2hr. The reaction mixture was cooled to rt and extracted with CH2CI2 (2 x 50 mL). The combined CH2CI2 extracts were washed with brine and dried over Na2S04. Evaporation of the solvent afforded 775 mg of a mixture of 1-methyl- and 2-methy-7-bromoindazoles which were separated by flash chromatography on Si02 using EtOAchexane (1:2) which afforded 251 mg (45%) of 7-bromo-2-methylindazole (4). Step 6:7-(2,4-Dichloro-phenyl)-2-methyl-2H-indazole (4a) - 7-Bromo-2-methylindazole - (4; 251 mg, 1.19 mmol) and Pd(PPh3)4(0) (42 mg, 0.035 mmol) were stirred in 5.5 mL DME under an Ar atmosphere for 30 min. 2,4-Dichlorobenzeneboronic acid (454 mg, 2.38 mmol) was added, followed immediately by 5.25 mL of 2 M NaaC03 solution. The mixture was heated at a gentle reflux for 2 hr, then cooled to rt and diluted with EtOAc (50 mL). The mixture was then washed with brine and dried over MgSO^ Evaporation of the solvent afforded a dark oil which was flash chromatographed on SiC>2 and eluted with EtOAchexane (1:2) which afforded 296 mg (90%) of 4a as a colorless viscous liquid. Step 7:4-[7-(2?4-Dichloro-phenyl)-2-methyl-2H-indazol-3-yl]-heptan-4-ol (5a) - Ind-azole 4a (292 mg, L05 mmol) was dissolved in 5mL dry THF under N2 and cooled to —78°. n-BuLi (0.51 mL of 2.5 M hexane solution, 1.26 mmol) was added dropwise via syringe, then stirred at -78° for 45 min. Heptanone (0.22 mL, 180 mg, 1.58 mmol) was added dropwise and the reaction then allowed to warm to rt The reaction mixture was diluted with EtOAc (50 mL), washed successively with 50% safd. NH4CI soln and brine, then dried over MgSO*. Evaporation of the organic phase afforded crude material which was flash chromatographed on SiC>2 and eluted with EtOAcihexane (1:3) to afford 152 mg (37%) of 5a. Step 8:7-(2,4-DicUoro-phenyl)-2-methyl-3-(l-propyl-but-l-enyl)-2H--indazole hydrochloride (la; Scheme 3, 6a) - Indazole 5a (220 mg, 0.56 mmol) and pTsOH"H20 (27 mg, 0.14 mmol) were combined in 8 mL dry PhMe under an N2 atmosphere and heated at reflux for 4 hrs. The reaction mixture was cooled to rt, diluted with EtOAc (25 mL) then washed successively with sat'd. NaHC03 solution and brine, then dried over MgS04-Evaporation afforded 215 mg of crude product which was flash chromatographed on Si02 and eluted with EtOAcihexane (1:4) to afford 195mg (93%) of the free base of la as a viscous oil. The oil was dissolved in Et20 (2 mL) and treated with 1.0 mL of 1.0 M HCl soln in Et20 to afford la as a white solid (150 mg; 65%) Example 2: 2-Methyl-3-(l-propyl-but-l-enyl)-7-(2,4,6-trimethyl-phenyl)-2H-indazole Hydrochloride (lb) Step 2: 7-(254-Dichloro-phenyl)-2-methyl-2H-indazol-3-ylamine (8a) - Nitroindazole 7a and 10 mg of 10% Pd on C were combined in 7 mL of MeOH then stirred under a hydrogen atmosphere (1 atm) overnight. Filtration of the catalyst and evaporation of the solvent afforded 70 mg of 8a, which was used in the next step without further purification. Step 3: N-[7-(2>4-Dichloro-phenyl)-2-methyl-2H-indazol-3-yl]-propionarnide (22a) -Amine 8a (70 mg, 0.23 mmol) and TEA (0.037 mL, 26 mg, 0.26 mmol) were dissolved in methylene chloride (3 mL) under a N2 atmosphere and cooled in an ice bath. Propionyl chloride (0.022 mL, 24 mg, 0.26 mmol) was added and then allowed to warm to rt. When the reaction was complete, the mixture was evaporated and the residue flash chromato-graphed (ethyl acetaterhexane, 1:1) to afford 68 mg (82%) of 22a. Step 4: [7-(2,4-Dichloro-phenyl)-2-methyl-2H-indazol-3-yl]-propyl-amine (23a) -Amide 22a (68 mg, 0.19 mmol) was dissolved in 5 mL dry THF under a N2 atmosphere. A 1M BH3-THF solution (0.40 mL, 0.40 mmol) was added all at once and the mixture heated at reflux for 2 hr, cooled to rt and 1 mL 6N HCl was cautiously added, and the mixture was reheated at reflux for 1 hr, and then cooled to rt. The mixture was made basic with 6N NaOH solution, then extracted with methylene chloride (2 x 25 mL). The combined extracts were washed with brine and dried over Na2S04. Evaporation of the solvent afforded 71 mg of 23a as a light brown viscous liquid, which was used without further purification. Step 5: [7-(2,4-Dichloro-phenyl)-2-methyl-2H-indazol-3-yl]-dipropyl-amine hydrochloride (24a or Id) - Amine 23a and propionaldehyde (0.032 mL, 26 mg, 0.44 mmol) were combined in 3 mL of DCE under nitrogen and allowed to stir at rt for 10 min. Na(OAc)3BH (102 mg, 0.48 mmol) was added all at once and the reaction mixture stirred at rt overnight^' The reaction mixture was diluted with 20 mL methylene chloride and washed with dilute NH4OH solution. The CH2CI2 solution was separated and dried (Na2S04). Evaporation of the solvent afforded a residue which was purified by flash chromatography (EtOAc:hexane, 1:9) to afford 27.4 mg of the free base of Id as a viscous liquid. The free base was dissolved in 1 mL ether and treated with 0.1 mL 2M HCl in ether solution which afforded 22 mg of Id as a white solid. Example 5: [2-Methyl-7-(2,4,6-trimethyl-phenyl)-2H-indazol-3-yl]-dipropyl-amm hydrochloride (Ic) saturated sodium bicarbonate solution, brine and dried over magnesium sulfate. The organic phase was concentrated to afford 19b as a light pink solid (0.16g; 78%). Step 2: (2-Metho;^-ethyl)-[2-me%l-7-(20b)-2-Methoxy-N-[2-methyl-7-(2,4,6-M^ (19b; 0.16 g, 0.47 mMol) was dissolved in 7 mL dry THF under a nitrogen atmosphere. A 1M solution of borane-THF complex in THF (0.95 mL, 0.95 mMol) was added all at once and the mixture heated at reflux for 2 hours, then cooled to rt. The reaction mixture was then acidified with 10% HCl aqueous solution and extracted with ethyl acetate (2 x 50 mL). The combined extracts were washed with 1M NaOH, water, brine, and dried over magnesium sulfate. The solvent was evaporated and the residue was flash chromato-graphed on silica eluting with hexane: acetone (9:1) to afford 20b as a light yellow semisolid (0.072g; 47%). Step 3: (2-Mefhoxy-ethyl)-[2-methyl-7-(2,4,6-trimethyl-phenyl)-2H-indazol-3-yl]-prop-yl-amine hydrochloride (le) - To a solution of (2-methoxy-ethyl)-[2-methyl-7-(2,4?6-tri-methyl-phenyl)-2H-indazol-3-yl]-amine (20b> 47 mg, 0.15 mMol) in 4 mL of DCE was added propionaldehyde (0.03 mL, 0.024 g, 0.42 mMol) followed a few minutes later by sodium triacetoxyborohydride (0.11 g, 0.52 mMol). The reaction was stirred at rt for four hours, then diluted with dichloromethane and washed with dilute aqueous ammonium hydroxide. The organic layer was dried over magnesium sulfate and concentrated. The residue was chromatographed on silica and eluted with an acetone/hexane gradient to provide the free base of the title compound as an oil (28 mg; 51%). The free base was dissolved in 1 mL ether and treated with 0.1 mL of 1.0 M HCl solution in ether to afford le as a light yellow powder (20mg). Ethyl-(2-methoxy-ethyl)-[2-m Hydrochloride (Ih) - To a solution of (2-methoxy-ethyl)-[2-methyl-7-(2>4,6-trimethyl-phenyl)-2H-indazol-3-yl]-amine (20b, 0.113 g, 0.35 mMol) in five mL of dichloroethane was added acetaldehyde (0.07 mL, 0.055 g> 1.25 mMol) followed a few minutes later by sodium triacetoxyborohydride (0.26 g, 1.23 mMol). The reaction mixture was stirred at room temperature for four hours, then diluted with dichloromethane and washed with dilute aqueous ammonium hydroxide. The organic phase was dried over magnesium sulfate and the solvent evaporated. The residue was chromatographed on silica gel and eluted with an acetone/hexane gradient to provide the free base of the title compound as an oil (72 mg; 58%). The free base was dissolved in 3 mL ether and treated with 0.25 mL of 1.0 M HCl solution in ether to afford Ih as a pink powder hydrochloride (65 mg). The following compounds were similarly prepared according to Example 6: cyclopropylmethyl-[2-me^ trifluoroacetic acid salt (Ip) faran-2-ylmethyl-[2-methy^ trifluoroacetic acid salt (Iq) [2-methyl-7-(2,4,6-trimethyl-phen^^ amine trifiuoro-acetic acid salt (Io) (a) MeOCH2COCl, TEA, THF (89%); (b) BH3THF IHF, reflux; (c) HC1, Etp (68%) Step 1:2-Me&oxy-N~(2-methoxy-ethyl)-N-^ indazol-3-yl]-acetamide (21b) - (2-Methoxy-ethyl)-[2-methyl-7-(234>6-trimetliyl-phenyl)-2H-indazol-3-yl]-amine (20b, 72 mg, 0.22 mMol) and TEA (0.033 mL, 0.024 g, 0.24 mMol) were dissolved in dichloromethane (3 mL) under a nitrogen atmosphere and cooled in an ice bath. Methoxyacetyl chloride (0.02 mL, 0.024 g, 0.24 mMol) was added and the reaction mixture allowed to warm to rt and stirred for two hr. Reaction mixture was quenched with cold water, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate solution, brine and dried over magnesium sulfate. The solvent was evaporated to afford 70 mg (80%) of 21b as an oil. Step 2: £i5-(2-methoxy-ethylH2~^^ amine hydrochloride(If) - 2-Methoxy-N-(2-methoxy-ethyl)-N-[2-methyl-7-(2,4,6-tri- methyl-phenyl)-2H-indazol-3-yl]-acetamide (21b, 70 mg, 0.18 mMol) was dissolved in 5mL of dry THF under nitrogen. A 1.0 M solution of BH3-THF complex (035 mL, 0.35 mMol) was added all at once and the mixture heated at reflux for 2 hr, then cooled to rt. The reaction mixture was acidified with 10% HC1 aqueous solution and extracted with then heated to 100 °C and stirred for 28 h. After the solution had cooled, 50 mL of ethyl acetate were added, and the solution was sequentially washed with 50 mL of water and 50 mL of a saturated aqueous NaCl solution, dried over MgS04, filtered, and concentrated to a yellow oil.' Column chromatography (0->33% EtOAc/hexanes) afforded 2.80 g (87%) of (7-bromo-2-methyl-2H-indazol-3-yl)-carbamic acid tert-butyl ester (32) as a pale yellow solid. Step 3: To a solution of (7-bromo-2-methyl-2H-indazol-3-yl)-carbamic acid tert-butyl ester (32; 0.092 g, 0.28 mmol) in 2.8 mL of dichloromethane was added 1.5 mL of tri-fluoroacetic acid. The solution was stirred for 5 h, then quenched with a 1 M aqueous NaOH solution. The mixture was extracted with three 10 mL portions of dichloromethane. The combined organic layers were dried over MgS04, filtered, and concentrated to 0.072 g (>100%) of crude 7-bromo-2-methyl-2H-indazol-3-ylamine. To this crude 7-bromo-2-methyl-2H-indazol-3-ylamine was added 7 mL of dichloroethane and propion-aldehyde (0.072 mL, 0.99 mmol), and the mixture was stirred for 10 min. Sodium triacet-oxyborohydride (0.237 g, 1.12 mmol) was added, and the mixture was stirred for 3 h. Additional propionaldehyde (0.097 mL, 1.3 mmol) was added, the mixture was stirred for 20 min., then additional sodium triacetoxyborohydride (0.320 g, 1.51 mmol) was added and the mixture was stirred for 19 h. Additional propionaldehyde (0.074 mL, 1.0 mmol) was added, the mixture was stirred for 1 h, then additional sodium triacetoxyborohydride (0.250 g, 1.18 mmol) was added and the mixture was stirred for 4 h. The mixture was partitioned between dichloromethane and a 1 M aqueous NaOH solution, and the aqueous layer was extracted with three 50 mL portions of dichloromethane. The combined organic layers were dried over MgS04, filtered, and concentrated to a brown oil. Column chromatography (0-^10% EtOAc/hexanes) afforded 0.062 g (62%) of (7-bromo-2-methyl-2H-indazol~3-yl)-dipropyl-amine (33). step 4: A mixture of (7-bromo-2-methyl-2H-indazol-3-yl)-dipropyl-amine (0.062 g, 0.20 mmol), tetra3ds(triphenylphosphine) palladium(O) (0.014 g, 0.012 mmol), 4-methoxy-2-methyl-3-pyridyl boronic acid (0.040 g, 0.24 mmol), 1 mL of N>N-dimethylformamide and 0.4 mL of a 2 M aqueous K3PO4 solution was stirred at 65 °C for 8.5 h. Solvents were removed in vacuo and the crude mixture was purified by reverse-phase HPLC to afford Ix. Example 10: 7-(2,4-DicUoro-phenyl)-2-methyl-2H-indazole-3-carboxylic acid cyclo-propylmethyl-propyl-amide Step 1: To a solution of 7-bromo-2-methyl-2H-indazole (34; 1.50 g, 7.12 mmol) in 50 mL of THE at -78° C was added a 2 M solution of lithium diisopropylamide (LDA) in THF/heptane/ ethylbenzene (43 mL, 8.6 mmol). The solution was stirred at 0-5° C for 15 min, then rechilled to -78° C. To the solution was added methyl chloroformate (0.66 mL, 8.5 mmol) all at once, and the mixture was stirred while slowly warm to room temperature over 19 h. The reaction was quenched with silica gel and concentrated. Column chromatography (0—»20% EtOAc/hexanes) afforded of 7-bromo-2-methyl-2H-indazole-3--carb-oxylic acid methyl ester (35a: 1.52g; 79%; m.p. 131-132) as a pale yellow solid. Step 2: A mixture of 35a (0.750 g, 2.79 mmol), 2,4-dichlorophenyl boronic acid (1.06 g, 5.57 mmol), 10 mL of ethylene glycol dimethyl ether, tetrakis(triphenylphosphine) palladium^) (0.097 g, 0.084 mmol), and 10 mL of a 2 M aqueous Na2CC>3 solution was stirred at 85 °C overnight, then allowed to cool. Ethyl acetate (50 mL) was added, and the mixture was washed with 30 mL of a saturated aqueous NaCl solution, dried over MgS04, filtered, and concentrated to a yellow oil. Column chromatography (0->10% EtOAc/-hexanes) afforded of 7-(2,4-dichloro-phenyl)-2-methyl-2H-indazole-3-carboxylic acid methyl ester (35b: 0.582g; 62%; m.p. 128-131) as a white solid. Step 3: To a solution of N"-propylcyclopropanemethyl amine (0.69 mL, 4.8 mmol) in 12 mL of benzene was slowly added a 2M solution of trimethylaluminum in heptane (2.4 mL, 4.8 mmol), and the solution was stirred for 75 min. The solution was transferred with a pipette to a solution of 35b (0.200 g, 0.597 mmol) in 10 mL of benzene. The solution was heated to 79°C, stirred for 2 d, then cooled to 0-5°C. A 2 M aqueous NaOH solution (20 mL) was slowly added, and the mixture was extracted with three 20 mL portions of di-chloromethane. The combined organic layers were washed with 40 mL of a saturated NaCl solution, dried over MgSO^ filtered, and concentrated to a brown oil. Column chromatography (0~>20% EtOAc/hexanes) afforded 7-(2,4-dichloro-phenyl)-2-methyl-2ff-indazole-3-carboxylic acid cyclopropylmefhyl-propyl-amide (35c: 0.117g; 47%) as an oil. combined organic layers were dried over MgSO^ filtered, and concentrated to a brown oil. Column chromatography (0^-8% EtOAc/hexanes) afforded 1.47 g (89%) of 7-bromo-2- methyl-3-((E)-l-propyl-but-l-enyl)-2H-indazole(37a). step 3: A mixture of 7-bromo-2-methyl-3-((E)-l-propyl-but-l-enyl)-2H-indazole (37a; 1.47 g, 4.79 mrnol), 2,4-dichlorophenyl boronic acid (1.32 g, 6.94 mmol), 18 mL of ethylene glycol dimethyl ether, tetrakis(triphen}dphosphine)palladium(0) (0.166 g, 0.143 . mmol) and 20 mL of a 2 M aqueous Na2CC>3 solution was stirred at 85 °C overnight, then allowed to cool. Ethyl acetate (50 mL) was added, and the mixture was washed with two 40 mL portions of a saturated aqueous NaCl solution. The combined aqueous layers were extracted with 20 mL of ethyl acetate. The combined organic layers were dried over Na2S04> filtered, and concentrated to a brown oil. Column chromatography (0-^-5% EtOAc/hexanes) afforded 1.57 g (88%) of 7-(2,4-dichloro-phenyl)-2-methyl-3-((E)-l-propyl-but-l-enyl)-2ff-indazole (37b) as a white solid. Example 12: PHARMACEUTICAL COMPOSITIONS Composition for Oral Administration The ingredients are combined and granulated using a solvent such as methanol. The formulation is then dried and formed into tablets (containing about 20 mg of active compound) with an appropriate tablet machine. Composition for Oral Administration All of the ingredients, except water, are combined and heated to about 60°C with stirring. A sufficient quantity of water at about 60°C is then added with vigorous stirring to emulsify the ingredients, and water then added q.s. about 100 g. Nasal Spray Formulations Several aqueous suspensions containing from about 0.025-0.5 percent active compound are prepared as nasal spray formulations. The formulations optionally contain inactive ingredients such as, e.g., macrocrystalline cellulose, sodium carboxymethylcellulose, dextrose, and the like. Hydrochloric acid maybe added to adjust pH. The nasal spray formulations may be delivered via a nasal spray metered pump typically delivering about 50-100 microliters of formulation per actuation. A typical dosing schedule is 2-4 sprays every 4-12 hours. Example 13: Intracellular cAMP Stimulation Assay Human Y-79 retinoblastoma cells are grown in RPMI1640 medium with 15% FBS. Measures of cAMP accumulation are performed by using NEN Adenylyl Cyclase Flash-Plate kit (SMP004). The cells are separated from culture medium, washed twice with PBS (150 Xg, 8 min), resuspended (2E+6 cells/ml) in Stimulation Buffer (provided in the kit), and then added to 96-well FlashPlates, (50,000 cells per well). Various concentrations of test compounds are incubated with the cells for 20 min prior to the addition of hCRF (30 nM). The total assay volume is 100 □!. The assay is terminated after 20 min after addition ofthehCRF by addition of Detection Buffer and [125I]cAMP. After 2 hr at rt the mixtures are aspirated and the bound radioactivity is measured with a Packard TopCount. The potency (IC5o values) of test compounds in inhibiting the hCRF-stimulated accumulation of cAMP is determined by nonlinear regression analyses with interactive cuive-fitting procedures. Example 14: CRF Receptor Binding Assay Human IMR-32 neuroblastoma cells are grown to 80% confluence in MEM medium containing 10% heat-inactivated FBS, ImM Sodium Pyruvate, and O.lmM nonessential amino acids. Cell membranes are prepared according the method of Dieterich and DeSouza (1996). The cells (-5E+9) are resuspended in 10 volumes of wash buffer (5 mM Tris HC1, 10 rnM MgCl2> 2 mM EGTA, pH 7.4 at RT), homogenized with a Polytron, and then cen-trifuged at 45,000 G for 20 min at 4°C. The membrane pellets are washed twice with wash buffer (45,000 G for 20 min at 4°C) and then resuspended (50 mM Tris HC1,10 mM MgCl2> 2 mM EGTA, pH 7.4 at RT). Protein concentration is determined using Pierce reagents and BSA as standard. Aliquots of 1-1.5 mL are stored at -80°C until binding assay. The competition binding assay is performed in a final volume of 250 jil, which contains assay buffer (50 mM Tris-HCl, 10 mM MgCl2, 2 mM EGTA, 0.2% BSA, O.lmM bacitracin and 100 klU/mL aprotinin pH 7.2 at R.T.), 0.05 nM [125I]Tyr°-ovine CRF (Du Pont New England Nuclear), 50 |ig of membrane protein, and test compound at various concentrations. Non-specific binding is determined with 1 uM hCRF. Binding reactions are terminated after 2 hr incubation at 25°C by filtering through 96-w GF/C filter plate using a Packard Harvester (Filtermate 196). The 96-w filter plate is pre-treated with 0.3% poly-ethyleneimine and pre-washed with washing buffer (50 mM Tris-HCl, 10 mM MgC^, 2 mM EGTA, 0.2% BSA, pH 7.2 at 4°C). Unbound radioactivity is removed by four rapid washes (0.8 ml/well) with wash buffer. The radioactivity is quantified using a Packard TopCount Data are analyzed using non-linear iterative curve fitting to obtain IC50 and Hill slope values. PKi values are derived from pIC5o values (-log of IC50). The compounds of the present invention were active in receptor binding and functional assays. The pICso of representative examples in the CRF1 functional assay are shown in Table 2: The features disclosed in the foregoing description, or the following claims, or the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for attaining the disclosed result, as appropriate, may, separately, or in any combination of such features, be utilized for realizing the invention in diverse forms thereof. The foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding. It will be obvious to one of skill in the art that changes and modifications may be practiced within the scope of the appended claims. Therefore, it is to be understood that the above description is intended to be illustrative and not restrictive. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the following appended claims, along with the full scope of equivalents to which such claims are entitled. All patents, patent applications and publications cited in this application are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual patent, patent application or publication were so individually denoted. alkyl, aminocarbonylalkyl, cyanoalkyl, Cs-gheterocyclyl, heterocyclylalkyl, aryl, aryl-alkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Ci-3 alkyl, and Q_3 alkyl substituted -with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q_6 alkyl, haloalkyl, Q_6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkyl-sulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or tu 1 in Ra andRD are taken together with the nitrogen to which they ar(e attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetxahydroquinoline, 1,2,3,4- tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, ^piperazine, morpholine* imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, amino- sulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from Q-e alkyl, haloalkyl, Q_6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group; or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutical^ acceptable salts thereof 2. A compound of Formula I: wherein: R1 is -NRaRb, -CRcRdRe, C02R\ or ~C(0)NRaRb; or R1 is hydrogen, cycloalkenyl, aryl, or heteroaryl, where each aryl or heteroaryl is optionally substituted with one or more substituents independently selected from Ci_e alkyl, Q_6 alkoxy, Q-6 alkylthio, Q_6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, -C(0)NRaRb,> and -NRaRb', where Ra' and RD are each independently selected from the group consisting of hydrogen, Ci_9 alkyi, and C1.9 alkylcarbonyl; R is hydrogen, C1-6 alkyi, Cs-e cycloalkyl, C3.6 cycloalkyl-Ci_3 alkyl, Q_6 alkylcarbonyl, Q_6 alkylsulfonyl, aryl, or arylalkyl, wherein said aryl or arylalkyl is optionally substituted with one or more substituents independently selected from QMS alkyl, haloalkyl, Q_6 alkoxy, and halogen; R is aryl or heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of Q_6 alkyl, Q-e alkoxy, Q.6 alkylthio, Ci_6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, tl ill H v» halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, Q.9 alkyl, and Q.9 alkylcarbonyl; Ra and RD are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, Ci_6 alkoxyalkyl, Q_6 alkylthioalkyl, carboxyalkyl, acyl, C3_6 cycloalkyl, C3_6 cycloalkyl-Ci_3 alkyl, di-C3_6 cycloalkylCi-3 alkyl, Ci_6heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, Cs-gheterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, haloalkyl, Ci_s alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfon-yloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or Ra and Rb are taken together with the nitrogen to which they are attached form an hetero-cyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-isoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfqnylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from Ci_6 alkyl, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group; R is hydrogen, hydroxy, C^6 alkoxy, or -NR R ; Rd and Re are each independently selected from the group consisting of hydrogen, Ci_9 alkyl, hydroxyalkyl, Q.6 alkoxyalkyl, Q^alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-Ci.3 alkyl, di-C3-6 ^cloalkyl-C^ alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Q^alkyl, and Q_3 alkyl substituted with both a C3.6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q.g alkyl, haloalkyl, Q-ealkoxy, amino, alkylamino, dialkylamino, and halogen; or RcandRd are taken together to form a divalent group selected from Ci.6 alkylidenyl, Cue heteroalkylidenyl, C3.6 cycloalkylidenyl, C3-6cycloalkyl-alkylidenyl, C3-6 cycloalkyl-Ci_3 alkyl-alkylidenyl, C3_6heterocyclylidenyl, C3„6heterocydyl~Ci-3 alkylidenyl, C3^hetero-cyclylaHcyl-Ci_3 alkylidenyl, aryl-Ci.3 alkylidenyl, aryl-Q_3 alkyl-alkylidenyl, heteroaryl-Ci_3 alkylidenyl, and heteroarylalkyl-Ci-3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from C^e alkyl, haloalkyl, Ci„6 alkoxy, amino, alkylamino, dialkylamino, and halogen; or Rd and Re are taken together with the carbon to which they are attached to form a cycloalkyl or heterocyclyl ring; «'" V.'11 R and R are each independently selected from the group consisting of hydrogen, Q-9 alkyl, hydroxyalkyl, Ci_6 alkoxyalkyl, Q-g alkylthioalkyl, carboxyalkyl, acyl, C^6 cycloalkyl, C3.6 cycloalkyl-Ci_3 alkyl, di-C3_6 cycloalkyl-Q^ alkyl, Ci_6 heteroalkyl, amino-alkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, aryl-alkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Q_3 alkyl, and C1-3 alkyl substituted with both a C3.6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-g alkyl, haloalkyl, Q_6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkyl-sulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or HI 1 HI Ra andRD are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidihe, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazohne, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, amino- neieroaryi, nexeroaryiaiKyi, pfrenyiaiKyi> cupkenyiaJJcyl, and Ci_3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C^6 alkyl, haloalkyl, Q_6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulf-onyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or Ra and Rb are taken together with the nitrogen to which they are attached form an hetero-cyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-isoquinoline, tetrahydxopyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C3-6 alkyl, haloalkyl, Q_6 alkoxy> amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group,- HI tni R is hydrogen, hydroxy, Ci_$ alkoxy, or -NR R ; Rd and Re are each independently selected from the group consisting of hydrogen, Q-9 alkyl, hydroxyalkyl, Ci_6 alkoxyalkyl, C1-6 alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3.6 cycloalkyI-Q-3 alkyl, di-Cs^cycloalkyl-Q^alky^ aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Q_3alkyl, and C^s alkyl substituted with both a 0$-$ cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Ci_g alkyl, haloalkyl, d-6 alkoxy, amino, alkylamino, dialkylamino, and halogen; or Rc and Rd are taken together to form a divalent group selected from C^e alkylidenyl, Q-e heteroalkylidenyl; C3-6 cycloalkylidenyl, C3-6 wherein: R1 is -NRaRb, -CRcRdRe, C02Ra; or, R1 is hydrogen, cycloalkenyl, aryl, or heteroaryl, where each aryl or heteroaryl is optionally substituted with one or more substituents independently selected from Cue alkyl, Cu6 alkoxy, Ci-6 alkylthio, Ci_6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, -C(0)NHaRb', and -NRaRb', where Ra' and Rb' are each independently selected from the group consisting of hydrogen, Q.9 alkyl, and Q. 9 aikylcarbonyl; R2 is hydrogen, Ci.6 allcyl, C3-6 cycloalkyl, C3_6 cycloalkyl-Ci„3 alkyl, Cue aikylcarbonyl, Cue alkylsulfonyl, aryl, or arylalkyl, wherein said aryl or arylalkyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl, haloalkyl, Cu6 alkoxy, and halogen; R is aryl or heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of Cue alkyl, Cue alkoxy, Q_6 alkylthio, Ci_6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and -NR R , where R and R are each independently selected from the group consisting of hydrogen, Cus alkyl, and Cu9 aikylcarbonyl; Ra and Rb are each independently selected from the group consisting of hydrogen, Cu 9alkyl, hydroxyalkyl, Cue alkoxyalkyl, Ci_6 alkylthioalkyl, carboxyalkyl, acyl, C3.6 cyclo-alkyl, Q_6 cycloalkyl-Q.3 alkyl, di-C^ecycloaikYlCi^ alkyl, Ci.6heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C$-z heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and Ci_3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Cue alkyl, haloalkyl, Cue alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfon-yloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or Ra and Rb are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-isoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazohne, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, arninocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from Ci-6 alkyl, haloalkyl, Ci-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl> morpholinyl, or piperazinyl group; III -L"' R is hydrogen, hydroxy, Q_6 alkoxy, or -NR R ; RdandRe are each independently selected from the group consisting of hydrogen, Q_ 9alkyl, hydroxyalkyl, Q-e alkoxyalkyl, Ci_6alkyltihioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3_6 cycloalkyl, C3_6 cycloalkyl-Q-3 alkyl, di-C3.6cycloalkyl-Ci.3 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Ci_3 alkyl, and C^s alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-e alkyl, haloalkyl, Q_e alkoxy, amino, alkylamino, dialkylamino, and halogen; or RcandRd are taken together to form a divalent group selected from Q .6 alkylidenyl, Q_6 ; heteroalkylidenyl, C3_6 cycloalkylidenyl, C3-6 cycloalkyl-alkylidenyl, C3_6 cycloalkyl-Ci_3 alkyl-alkylidenyl, C3.6 heterocyclyhdenyl, C3-6heterocyclyl-Ci_3 alkylidenyl, C3_6hetero-cyclylalkyl-Q-3 alkylidenyl, aryl-Ci-3 alkylidenyl, aryl-Q„3 alkyl-alkylidenyl, heteroaryl-Ci_3 alkylidenyl, and heteroarylalkyl-Ci_3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from Q-e alkyl, haloalkyl, Q-e alkoxy, amino, alkylamino, dialkylamino, and halogen; or RQ and Re are taken together with the carbon to which they are attached to form a cycloalkyl or heterocyclyl ring; Ra andRD are each independently selected from the group consisting of hydrogen, Q-9 alkyl, hydroxyalkyl, Ci-$ alkoxyalkyl, Q-e alkylthioalkyl, carboxyalkyl, acyl, C3_6 cycloalkyl, C3-6 cycIoalkyl-Ci-3 alkyl, di-C3-6 cycloalkyl-Ci_3 alkyl, Q-g heteroalkyl, amino-alkyl, amino carbonylalkyl, cyano alkyl, C5_g heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-Ci-3 alkyl, and Ci_3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl," phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of Q-g alkyl, haloalkyl, Que alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkyl-sulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl; or Ra andRD are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4- tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, amino-sulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from Chalky!, haloalkyl, Q-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstitu-ted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piper-azinyl group; or, individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutical^ acceptable salts thereof; with the proviso that if R1 is -CRCR Re, R2 is hydrogen or alkyl, R3 is a 5- or 6-membered heteroaromatic ring, and (i) Rc is hydrogen and one of Rd and Re is hydrogen or alkyl, then the other of Rd and Re is other than hydrogen or alkyl if the number of carbon atoms in R and Re together are zero to three; or, (ii) Rcis hydrogen and one of R and Re is hydrogen or alkyl, then the other of R and Re is other than alkoxy, alkoxyalkyl, heterocyclyl, heterocyclylalkyl, or heteroalkyl; or, ttt Lin in ^111 in (iii) Rcis NRa Rb and one of Ra and Rb is hydrogen or CU3 alkyl, then the other of Ra V til and R is other than hydrogen or Ci_3 alkyl. 5. The compound of formula I according to claim 1 wherein R1 is -NRaRb, -CRcRdRe, C02Ra> or -C(0)NRaRb. 6. The compound of formula I according to claim 1 wherein R is Q-e alkyl. 7. The compound of formula I according to claim 1 wherein R is aryl or heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of Q-6 alkyl, Q-e alkoxy and halogen. 8. The compound of formula I according to claim 1 selected from 7-(2,4-dicHoro-phenyl)-2-methyl-3-^ 2-methyl-3-(l-propyl-but-l-enyl)-7-(2,4^ 3-(3-methoxy-l-me1hoxymethyl^ 2H-indazole hydrochloride, [7-(2,4-dichloro-phenyl)-2-melhyl-2H-indazol-3-yl]-dipropy cyclopropylmethyl-[7-(2,4-dicHoro-^^ hydrochloride, cyclopropylmethyH7-(2,4-dic^ amine trifiuoroacetate, [7- (2,4-dimethoxy-phenyl)-2-methyl-2H-indazol-3-yl] -dipropyl-amine hydrochloride, 4-({[2-met±iyl-7-(2,4,6-tri^ benzonitrile trifiuoroacetate, benzyl-[2-methyl-7-(2,4,6-trimethyl^^ acetate, 7-(6-methox7-2-melhyl-pyridin-3-yl)-2-methyl-3-((E)-l-propyl-but-l- hydrochloride, dimethyl-{4-methyl-5-[2-methyl-3-(^ 2-yl}-amine trifiuoroacetate, [2-methyl~7-(2,4,6~trimethyl-phenyl)-2H^^ trifiuoroacetate, (3)4-dimethoxy^-benzyl)-[2-methyl-7-(2,4,6-trimethyl-phenyl)-2H-indazol-3-yl] -propylamine trifiuoroacetate and 7-(2,4-dichloro-phenyl)-2-methyl-3-morpholin-4-ylmethyl-2H-indazole. 9. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of formula I or II according to claim 1 or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof; in admix ture with at least one pharmaceutically acceptable carrier. 10. A method for treating a subject having a disease state that is alleviated by treatment with a CRF receptor antagonist, which comprises administering to such a subject a thera peutically effective amount of a compound of formula I or II according to claim 1 or in dividual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof. 11. The method of claim 10, wherein the disease state is selected from the group consisting of phobias, stress-related illnesses, mood disorders, eating disorders, generalized anxiety disorders, stress-induced gastrointestinal dysfunctions, neurodegenerative diseases, and neuropsychiatric disorders.

Documents:

1086-chenp-2005 abstract duplicate.pdf

1086-chenp-2005 claims duplicate.pdf

1086-chenp-2005 description (complete) duplicate.pdf

1086-chenp-2005-abstract.pdf

1086-chenp-2005-claims.pdf

1086-chenp-2005-correspondnece-others.pdf

1086-chenp-2005-correspondnece-po.pdf

1086-chenp-2005-description(complete).pdf

1086-chenp-2005-form 1.pdf

1086-chenp-2005-form 26.pdf

1086-chenp-2005-form 3.pdf

1086-chenp-2005-form 5.pdf

1086-chenp-2005-form18.pdf

1086-chenp-2005-pct.pdf