Pyrazole compounds useful as protein kinase inhibitors

1. A compound of formula VII:

or a pharmaceutically acceptable salt thereof, wherein:

G is Ring C or Ring D;

Ring C is selected from a phenyl ring, wherein said Ring C has one or two ortho substituents independently selected from —R 1 , any non-oxtho carbon position on Ring C is independently substituted by H or —R 5 , and two adjacent substituents on Ring C are optionally taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-6 membered ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, said fused ring being optionally substituted by halo, oxo, or —R 8 ;

Ring D is a 5-7 membered monocyclic aryl ring or 8-10 membered bicyclic aryl ring, wherein Ring D is substituted at any substitutable ring carbon by H, oxo, or —R 5 , provided that when Ring D is a six-membered aryl ring, —R 5 is hydrogen at each ortho carbon position of Ring D;

R 1 is selected from -halo, —CN, —NO 2 , T-V-R 6 , phenyl, 5-6 membered heteroaryl ring, 5-6 membered heterocyclyl ring, or C 1-6 aliphatic group, said phenyl, heteroaryl, and heterocyclyl rings each optionally substituted by up to three groups independently selected from halo, oxo, or —R 8 , said C 1-6 aliphatic group optionally substituted with halo, cyano, nitro, or oxygen, or R 1 and an adjacent substituent taken together with their intervening atoms form said ring fused to Ring C;

R y is hydrogen or T-R 3″ ;

T is a valence bond or a C 1-4 alkylidene chain;

R 2 and R 2′ are taken together with their intervening atoms to form a fused, 5-8 membered, unsaturated or partially unsaturated, ring having 0-3 ring heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each substitutable carbon on said fused ring formed by R 2 and R 2′ is substituted by H, halo, oxo, —CN, —NO 2 , —R 7 , or —V—R 6 , and any substitutable nitrogen on said ring formed by R 2 and R 2′ is substituted by H or R 4 ;

R 3″ is selected from an optionally substituted monocyclic or bicyclic group selected from C 3-10 carbocyclyl, C 6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms;

each R as recited below is independently selected from hydrogen or an optionally substituted group selected from C 1-6 aliphatic, C 6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 5-10 ring atoms; wherein said aryl, heterocyclyl or heteroaryl

contains 1-4 heteroatoms selected from O, N, or S;

is monocyclic or bicyclic; and

each monocyclic ring, either alone or part of a bicyclic ring, contains 3-7 ring atoms;

each R 4 as recited below is independently selected from —R 7 , —COR 7 , —CO 2 (optionally substituted C 1-6 aliphatic), —CON(R 7 ) 2 , or —SO 2 R 7 , or two R 4 on the same nitrogen are taken together to form a 5-8 membered heterocyclyl or heteroaryl ring;

each R 5 is independently selected from —R, halo, —OR, —C(═O)R, —CO 2 R, —COCOR, —NO 2 , —CN, —S(O)R, —SO 2 R, —SR, —N(R 4 ) 2 , —CON(R 4 ) 2 , —SO 2 N(R 4 ) 2 , —OC(═O)R, —N(R 4 )COR, —N(R 4 )CO 2 (optionally substituted C 1-6 aliphatic), —N(R 4 )N(R 4 ) 2 , —C═NN(R 4 ) 2 , —C═N—OR, —N(R 4 )CON(R 4 ) 2 , —N(R 4 )SO 2 N(R 4 ) 2 , —N(R 4 )SO 2 R, or —OC(═O)N(R 4 ) 2 ;

V is —O—, —S—, —SO—, —SO 2 —, —N(R 6 )SO 2 —, —SO 2 N(R 6 )—, —N(R 6 )—, —CO—, —CO 2 —, —N(R 6 )CO—, —N(R 6 )C(O)O—, —N(R 6 )CON(R 6 )—, —N(R 6 )SO 2 N(R 6 )—, —N(R 6 )N(R 6 )—, —C(O)N(R 6 )—, —OC(O)N(R 6 )—, —C(R 6 ) 2 O—, —C(R 6 ) 2 S—, —C(R 6 ) 2 SO—, —C(R 6 ) 2 SO 2 —, —C(R 6 ) 2 SO 2 N(R 6 )—, —C(R 6 ) 2 N(R 6 )—, —C(R 6 ) 2 N(R 6 )C(O)—, —C(R 6 ) 2 N(R 6 )C(O)O—, —C(R 6 )═NN(R 6 )—, —C(R 6 )═N—O—, —C(R 6 ) 2 N(R 6 )N(R 6 )—, —C(R 6 ) 2 N(R 6 )SO 2 N(R 6 )—, or —C(R 6 ) 2 N(R 6 )CON(R 6 )—;

W is —C(R 6 ) 2 O—, —C(R 6 ) 2 S—, —C(R 6 ) 2 SO—, —C(R 6 ) 2 SO 2 —, —C(R 6 ) 2 SO 2 N(R 6 )—, —C(R 6 ) 2 N(R 6 )—, —CO—, —CO 2 —, —C(R 6 )OC(O)—, —C(R 6 )OC(O)N(R 6 )—, —C(R 6 ) 2 N(R 6 )CO—, —C(R 6 ) 2 N(R 6 )C(O)O—, —C(R 6 )═NN(R 6 )—, —C(R 6 )═N—O—, —C(R 6 ) 2 N(R 6 )N(R 6 )—, —C(R 6 ) 2 N(R 6 )SO 2 N(R 6 )—, —C(R 6 ) 2 N(R 6 )CON(R 6 )—, or —CON(R 6 )—;

each R 6 is independently selected from hydrogen, an optionally substituted C 1-4 aliphatic group, or two R 6 groups on the same nitrogen atom are taken together with the nitrogen atom to form a 5-6 membered heterocyclyl or heteroaryl ring;

each R 7 is independently selected from hydrogen or an optionally substituted C 1-6 aliphatic group, or two R 7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring;

each R 8 is independently selected from an optionally substituted C 1-4 aliphatic group, —OR 6 , —SR 6 , —COR 6 , —SO 2 R 6 , —N(R 6 ) 2 , —N(R 6 )N(R 6 ) 2 , —CN, —NO 2 , —CON(R 6 ) 2 , or —CO 2 R 6 ; and

R 9 is selected from -R, halo, —OR, —C(═O)R, —CO 2 R, —COCOR, —NO 2 , —CN, —S(O)R, —SO 2 R, —SR, —N(R 4 ) 2 , —CON(R 4 ) 2 , —SO 2 N(R 4 ) 2 , —OC(═O)R, —N(R 4 )COR, —N(R 4 )CO 2 (optionally substituted C 1-6 aliphatic), —N(R 4 )N(R 4 ) 2 , —C═NN(R 4 ) 2 , —C═N—OR, —N(R 4 )CON(R 4 ) 2 , —N(R 4 )SO 2 N(R 4 ) 2 , —N(R 4 )SO 2 R, or —OC(═O)N(R 4 ) 2 .

2. The compound according to claim 1 , wherein said compound has one or more features selected from the group consisting of:

(a) Ring C is an optionally substituted ring selected from phenyl, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring, and R 1 is -halo, an optionally substituted C 1-6 aliphatic group, phenyl, —COR 6 , —OR 6 , —CN, —SO 2 R 6 , —SO 2 NH 2 , —N(R 6 ) 2 , —CO 2 R 6 , —CONH 2 , —NHCOR 6 , —OC(O)NH 2 , or —NHSO 2 R 6 ; or Ring D is an optionally substituted ring selected from a phenyl or naphthyl ring;

(b) R y is T-R 3″ , wherein T is a valence bond or a methylene; and

(c) R 2 and R 2′ are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring.

3. The compound according to claim 2 , wherein:

(a) Ring C is an optionally substituted phenyl ring, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is selected from a naphthyl, quinolinyl or isoquinolinyl ring, and R 1 is -halo, an optionally substituted C 1-6 aliphatic group, phenyl, —COR 6 , —OR 6 , —CN, —SO 2 R 6 , —SO 2 NH 2 , —N(R 6 ) 2 , —CO 2 R 6 , —CONH 2 , —NHCOR 6 , —OC(O)NH 2 , or —NHSO 2 R 6 ; or Ring D is an optionally substituted ring selected from a phenyl, or naphthyl ring;

(b) R y is T-R 3″ , wherein T is a valence bond or a methylene; and

(c) R 2 and R 2′ are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring.

4. The compound according to claim 2 , wherein said compound has one or more features selected from the group consisting of:

(a) Ring C is an optionally substituted phenyl ring, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R 1 is -halo, a C 1-6 haloaliphatic group, a C 1-6 aliphatic group, phenyl, or —CN; or Ring D is an optionally substituted ring selected from phenyl or naphthyl;

(b) R y is T-R 3″ , wherein T is a valence bond or a methylene and R 3″ is an optionally substituted group selected from C 3-6 carbocyclyl, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring;

(c) R 2 and R 2′ are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and

(d) Ring D is substituted by oxo or R 5 , wherein each R 5 is independently selected from -halo, —CN, —NO 2 , —N(R 4 ) 2 , optionally substituted C 1-6 aliphatic group, —OR, —C(O)R, —CO 2 R, —CONH(R 4 ), —N(R 4 )COR, —SO 2 N(R 4 ) 2 , or —N(R 4 )SO 2 R.

5. The compound according to claim 4 , wherein:

(a) Ring C is an optionally substituted ring, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R 1 is -halo, a C 1-6 haloaliphatic group, a C 1-6 aliphatic group, phenyl, or —CN; or Ring D is an optionally substituted ring selected from phenyl or naphthyl;

(b) R y is T-R 3″ , wherein T is a valence bond or a methylene and R 3″ is an optionally substituted group selected from C 3-6 carbocyclyl, phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring;

(c) R 2 and R 2′ are taken together with their intervening atoms to form a substituted or unsubstituted benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring; and

(d) Ring D is substituted by oxo or R 5 , wherein each R 5 is independently selected from -halo, —CN, —NO 2 , —N(R 4 ) 2 , optionally substituted C 1-6 aliphatic group, —OR, —C(O)R, —CO 2 R, —CONH(R 4 ), —N(R 4 )COR, —SO 2 N(R 4 ) 2 , or —N(R 4 )SO 2 R.

6. The compound according to claim 4 , wherein said compound has one or more of the features selected from the group consisting of:

(a) R y is T-R 3″ , wherein T is a valence bond or a methylene and R 3″ is an optionally substituted group selected from phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring;

(b) Ring C is an optionally substituted phenyl ring, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R 1 is -halo, a C 1-4 aliphatic group optionally substituted with halogen, or —CN; or Ring D is an optionally substituted ring selected from phenyl or naphthyl;

(c) R 2 and R 2′ are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, —N(R 4 ) 2 , —C 1-4 alkyl, —C 1-4 haloalkyl, —NO 2 , —O(C 1-4 alkyl), —CO 2 (C 1-4 alkyl), —CN, —SO 2 (C 1-4 alkyl), —SO 2 NH 2 , —OC(O)NH 2 , —NH 2 SO 2 (C 1-4 alkyl), —NHC(O)(C 1-4 alkyl), —C(O)NH 2 , or —CO(C 1-4 alkyl), wherein the (C 1-4 alkyl) is a straight, branched, or cyclic alkyl group; and

(d) Ring D is substituted by oxo or R 5 , wherein each R 5 is independently selected from —Cl, —F, —CN, —CF 3 , —NH 2 , —NH(C 1-4 aliphatic), —N(C 1-4 aliphatic) 2 , —O(C 1-4 aliphatic), C 1-4 aliphatic, and —CO 2 (C 1-4 aliphatic).

7. The compound according to claim 6 , wherein:

(a) R y is T-R 3″ , wherein T is a valence bond or a methylene and R 3″ is an optionally substituted group selected from phenyl, or a 5-6 membered heteroaryl or heterocyclyl ring;

(b) Ring C is an optionally substituted phenyl ring, wherein when Ring C and two adjacent substituents thereon form a bicyclic ring system, the bicyclic ring system is a naphthyl ring, and R 1 is -halo, a C 1-4 aliphatic group optionally substituted with halogen, or —CN; or Ring D is an optionally substituted ring selected from phenyl or naphthyl;

(c) R 2 and R 2′ are taken together with their intervening atoms to form a benzo, pyrido, pyrimido or partially unsaturated 6-membered carbocyclo ring optionally substituted with -halo, —N(R 4 ) 2 , —C 1-4 alkyl, —C 1-4 haloalkyl, —NO 2 , —O(C 1-4 alkyl), —CO 2 (C 1-4 alkyl), —CN, —SO 2 (C 1-4 alkyl), —SO 2 NH 2 , —OC(O)NH 2 , —NH 2 SO 2 (C 1-4 alkyl), —NHC(O)(C 1-4 alkyl), —C(O)NH 2 , or —CO(C 1-4 alkyl), wherein the (C 1-4 alkyl) is a straight, branched, or cyclic alkyl group; and

(d) Ring D is substituted by oxo or R 5 , wherein each R 5 is independently selected from —Cl, —F, —CN, —CF 3 , —NH 2 , —NH(C 1-4 aliphatic), —N(C 1-4 aliphatic) 2 , —O(C 1-4 aliphatic), C 1-4 aliphatic, and —CO 2 (C 1-4 aliphatic).

8. The compound according to claim 7 , wherein said compound is selected from:

9. A composition comprising a compound according to any of claims 1 - 8 and a pharmaceutically acceptable carrier.