Pyrrolopyridine inhibitors of kinases

1. A compound having formula (I)

wherein

R 1a , R 1b , and R 1c are independently hydrogen, hydroxy, nitro, halogen, cyano, trifluoromethyl, trifluoromethoxy, C 1-4 -alkyl, —OR a , —NR b R c ; —C(O)OR a , —C(O)NR b R c , —NR b C(O)R c , —NHC(O)NHR b , or —NHSO 2 R a ;

X is CR 2 ;

R 2 is hydrogen or C 1-4 -alkyl;

Y is NR 3 R 4 , NR 6 C(O)R 7 , NR 6 SO 2 R 7 , aryl, or heterocyclyl, wherein the aryl and heterocyclyl are optionally substituted with one or more R 5 ;

R 3 is hydrogen, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-(C 1-8 -alkyl)-, heterocycloalkyl, heterocycloalkyl-(C 1-8 -alkyl)-, aryl, aryl-(C 1-8 -alkyl)-, heteroaryl-, or heteroaryl-(C 1-8 -alkyl)-, wherein (a) the R 3 C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl substituents, alone or as part of another group, are optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, nitro, —OR a , —C(O)R a , —C(O)OR a , —OC(O)R a , —NR b R c , —NR b C(O)R a , —NHC(O)NHR b , —C(O)NR b R c , —NHSO 2 R a , —SO 2 NR b NR c , and aryl; and (b) the R 3 C 3-8 -cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, alone or as part of another group, are optionally substituted with one or more R 5 ;

R 4 is hydrogen or C 1-8 -alkyl; wherein the C 1-8 -alkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, —OR a , —C(O)R a , —C(O)OR a , —OC(O)R a , —NR b R c , —NR b C(O)R a , —NHC(O)NHR b , —C(O)NR b R c , —NHSO 2 R a , and —SO 2 NR b NR c ;

R 5 is selected from the group consisting of C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, —OR d , —C(O)R d , —C(O)OR d , —OC(O)R d , —NR e R f , —NR e C(O)R d , —NHC(O)NHR e , —NHSO 2 R e , —C(O)NR e R f , —SR d , —S(O)R d , —SO 2 R d , —SO 2 NR e NR f , —B(OH) 2 , —CF 3 , —CF 2 CF 3 , —OCF 3 , and —OCF 2 CF 3 wherein (a) the R 5 C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, substituents are optionally substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, C 3-8 -cycloalkyl, halogen, cyano, nitro, —OR d , —C(O)R d , —C(O)OR d , —OC(O)R d , —NR e R f , —NR e C(O)R d , —NHC(O)NHR e , —C(O)NR e R f ; and wherein (b) the R 5 aryl or heterocyclyl substituents are optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, —OR g , —C(O)R g , —C(O)OR g , —OC(O)R g , —NR h R i , —NR h C(O)R g , —NHC(O)NHR h , —NHSO 2 R g , —C(O)NR h R i , —SR g , —S(O)R g , —SO 2 R g , —SO 2 NR h NR i , —CF 3 , —CF 2 CF 3 , —OCF 3 , and —OCF 2 CF 3 ;

R 6 is hydrogen or C 1-8 -alkyl;

R 7 is C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-(C 1-8 -alkyl)-, heterocycloalkyl, heterocycloalkyl-(C 1-8 -alkyl)-, aryl, aryl-(C 1-8 -alkyl)-, heteroaryl-, or heteroaryl-(C 1-8 -alkyl)-, wherein (a) the R 7 C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl substituents, alone or as part of another group, are optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, nitro, —OR a , —C(O)R a , —C(O)OR a , —OC(O)R a , —NR b R c , —NR b C(O)R a , —NHC(O)NHR b , —C(O)NR b R c , —NHSO 2 R a , —SO 2 NR b NR c , and aryl; and (b) the R 7 C 3-8 -cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, alone or as part of another group, are optionally substituted with one or more R 5 ;

R a , at each occurrence, is selected from the group consisting of hydrogen, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl, wherein the C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, halogen, cyano, hydroxy, C 1-8 -alkoxy, —NH 2 , —NH(C 1-8 -alkyl), —O(C 1-8 -alkyl)NH 2 , and —N(C 1-8 -alkyl) 2 ;

R b and R c , at each occurrence, are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl, and optionally, R b and R c can be joined together to form a 4-7 membered heterocycloalkyl ring, wherein the C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, halogen, cyano, hydroxy, C 1-8 -alkoxy, —NH 2 , —NH(C 1-8 -alkyl), and —N(C 1-8 -alkyl) 2 ;

R d , at each occurrence, is selected from the group consisting of hydrogen, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl, wherein the C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, aryl, aryl-(C 1-8 -alkyl)-, heterocyclyl, C 3-8 -cycloalkyl, halogen, cyano, oxo, hydroxy, C 1-8 -alkoxy, —NH 2 , —NH(C 1-8 -alkyl), and —N(C 1-8 -alkyl) 2 ; wherein the aryl, aryl-(C 1-8 -alkyl)-, heterocyclyl, and C 3-8 -cycloalkyl, alone or as part of another group, are optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, halogen, cyano, hydroxy, C 1-8 -alkoxy, —NH 2 , —NH(C 1-8 -alkyl), and —N(C 1-8 -alkyl) 2 ;

R e and R f , at each occurrence, are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl, and optionally, R e and R f can be joined together to form a 4-7 membered heterocycloalkyl ring, wherein the C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, halogen, cyano, hydroxy, C 1-8 -alkoxy, —NH 2 , —NH(C 1-8 -alkyl), and —N(C 1-8 -alkyl) 2 ;

R g , at each occurrence, is selected from the group consisting of hydrogen, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl, wherein the C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, halogen, cyano, hydroxy, C 1-8 -alkoxy, —NH 2 , —NH(C 1-8 -alkyl), and —N(C 1-8 -alkyl) 2 ;

R h and R i , at each occurrence, are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, and C 3-8 -cycloalkyl, and optionally, R h and R i can be joined together to form a 4-7 membered heterocycloalkyl ring, wherein the C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, aryl, heterocyclyl, C 3-8 -cycloalkyl, halogen, cyano, hydroxy, C 1-8 -alkoxy, —NH 2 , —NH(C 1-8 -alkyl), and —N(C 1-8 -alkyl) 2 ;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R 1a , R 1b , and R 1c are hydrogen.

3. The compound of claim 1 , wherein R 2 is hydrogen.

4. The compound of claim 1 , wherein Y is NR 3 R 4 .

5. The compound of claim 4 , wherein R 3 is C 1-8 -alkyl, wherein the C 1-8 -alkyl is optionally substituted with one or two R 5 .

6. The compound of claim 4 , wherein R 3 is aryl or heteroaryl, wherein the aryl and heteroaryl are optionally substituted with one or more R 5 .

7. The compound of claim 4 , wherein R 3 is C 3-8 -cycloalkyl or heterocycloalkyl, wherein the C 3-8 -cycloalkyl or heterocycloalkyl are optionally substituted with one or more R 5 .

8. The compound of claim 4 , wherein R 3 is C 3-8 -cycloalkyl-(C 1-8 -alkyl)-, heterocycloalkyl-(C 1-8 -alkyl)-, aryl-(C 1-8 -alkyl)-, or heteroaryl-(C 1-8 -alkyl)-, wherein the R 3 C 3-8 -cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more R 5 .

9. The compound of claim 4 , wherein R 4 is hydrogen or methyl.

10. The compound of claim 1 , wherein Y is heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more R 5 .

11. The compound of claim 1 , wherein Y is aryl, wherein the aryl is optionally with one or more R 5 .

12. The compound of claim 1 wherein R 1a , R 1b and R 1c are hydrogen, R 2 is hydrogen, Y is NR 3 R 4 , wherein R 3 is C 3-8 -cycloalkyl, wherein the C 3-8 -cycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of C 1-8 -alkyl, heterocyclyl, halogen, —OR d , —C(O)OR d , —NR e R f , —NR e C(O)R d , —NHSO 2 R e , —SO 2 R d , —CF 3 , and —OCF 3 wherein the C 1-8 -alkyl is optionally substituted with one or more —OR d , wherein R 4 is hydrogen or C 1-8 -alkyl, and wherein R d , R e , and R f are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, and C 3-8 -cycloalkyl.

13. The compound of claim 1 wherein R 1a , R 1b and R 1c are hydrogen, R 2 is hydrogen, Y is NR 3 R 4 , wherein R 3 is aryl, wherein the aryl is optionally substituted with one or two substituents independently selected from the group consisting of C 1-8 -alkyl, heterocyclyl, halogen, —OR d , —C(O)OR d , —NR e R f , —NR e C(O)R d , —NHSO 2 R e , —SO 2 R d , —CF 3 , and —OCF 3 wherein the C 1-8 -alkyl is optionally substituted with one or more —OR d , wherein R 4 is hydrogen or C 1-8 -alkyl, and wherein R d , R e , and R f are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, and C 3-8 -cycloalkyl.

14. The compound of claim 1 wherein R 1a , R 1b and R 1c are hydrogen, R 2 is hydrogen, Y is heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, heterocyclyl, halogen, —OR d , —C(O)OR d , —NR e R f , —NR e C(O)R d , —NHSO 2 R e , —SO 2 R d , —CF 3 , and —OCF 3 wherein the C 1-8 -alkyl is optionally substituted with one or more —OR d , wherein R 4 is hydrogen or C 1-8 -alkyl, and wherein R d , R e , and R f are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, and C 3-8 -cycloalkyl.

15. The compound of claim 1 wherein R 1a , R 1b and R 1c are hydrogen, R 2 is hydrogen, Y is NR 3 R 4 , wherein R 3 is C 1-8 -alkyl, wherein the R 3 C 1-8 -alkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, —OR a , and —NR b R c ; wherein R 4 is hydrogen or C 1-8 -alkyl, and wherein R c , R d , R e , and R f are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, and C 3-8 -cycloalkyl.

16. The compound of claim 1 wherein R 1a , R 1b , and R 1c are hydrogen, R 2 is hydrogen, Y is aryl, wherein the aryl is optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, heterocyclyl, halogen, —OR d , —C(O)OR d , —NR e R f , —NR e C(O)R d , —NHSO 2 R e , —SO 2 R d , —CF 3 , and —OCF 3 wherein the C 1-8 -alkyl is optionally substituted with one or more —OR d , wherein R 4 is hydrogen or C 1-8 alkyl, and wherein R d , R e , and R f are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, and C 3-8 -cycloalkyl.

17. The compound of claim 1 wherein R 1a , R 1b and R 1c are hydrogen, R 2 is hydrogen, Y is heteroaryl, wherein the heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of C 1-8 -alkyl, heterocyclyl, halogen, —OR d , —C(O)OR d , —NR e R f , —NR e C(O)R d , —NHSO 2 R e , —SO 2 R d , —CF 3 , and —OCF 3 wherein the C 1-8 -alkyl is optionally substituted with one or more —OR d , wherein R 4 is hydrogen or C 1-8 -alkyl, and wherein R d , R e , and R f are independently selected from the group consisting of hydrogen, C 1-8 -alkyl, and C 3-8 -cycloalkyl.

18. The compound of claim 1 which is

6-phenyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-[3-(trifluoromethoxy)phenyl]pyridin-2(1H)-one;

4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-[3-(trifluoromethyl)phenyl]pyridin-2(1H)-one;

6-(2,3-dimethylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-(2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-(1,3-benzodioxol-5-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-(3-thienyl)pyridin-2(1H)-one;

6-(2-naphthyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-(3-chlorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-(2,3-dimethoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-(2-fluoro-3-methoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-(4-chloro-2-fluorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-[2-methoxy-5-(trifluoromethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

2′-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3′-bipyridin-6(1H)-one;

6-(3-chloro-2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

3′-chloro-2′-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,4′-bipyridin-6(1H)-one;

6-[3-(morpholin-4-yl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-[3-(methylsulfonyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-(1H-pyrazol-4-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

2′-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3′-bipyridin-6(1H)-one;

6-[(3-methoxyphenyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-anilino-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

6-[(trans-4-aminocyclohexyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;

N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)cyclopropanesulfonamide;

N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)cyclopropanecarboxamide; or

1-(4-fluorobenzyl)-N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)azetidine-3-carboxamide.

19. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 1 and pharmaceutically acceptable excipient.