Pyrrolopyrazine kinase inhibitors

1. A compound of Formula I

R is R 1 , R 2 , R 3 , or R 4 ;

R 1 is lower alkyl, lower alkoxy, phenyl, benzyl, heteroaryl, cycloalkyl, heterocycloalkyl, or cycloalkylalkyl, optionally substituted with one or more R 1a ;

R 1a is R 1b or R 1c ;

R 1b is halogen, oxo, hydroxy, or —CN;

R 1c is —C(═O)O(R 1f ), —C(═O)CH 2 (R 1e ), —S(R 1f ), —S(O) 2 (R 1f ), or —S(═O) (R 1f ), lower alkyl, lower alkoxy, amino, amido, lower haloalkyl, phenyl, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkyloxy, or heterocycloalkyloxy optionally substituted with one or more R 1d ;

R 1d is H, halogen, hydroxy, lower alkyl, lower alkoxy, or lower haloalkyl;

R 1e is H, lower alkyl, lower alkoxy, —CN, lower haloalkyl, phenyl, heteroaryl, cycloalkyl, or heterocycloalkyl;

R 1f is H, lower alkyl, lower haloalkyl, phenyl, heteroaryl, cycloalkyl, or heterocycloalkyl;

R 2 is N(R 2a ) 2 ;

each R 2a is independently H or R 2b ;

each R 2b is independently lower alkyl, phenyl, heteroaryl, cycloalkyl, heterocycloalkyl, or heterocycloalkyl alkylene, optionally substituted with one or more R 2c ;

R 2c is R 2d or R 2e ;

 R 2d is halogen, oxo, or hydroxy;

 R 2e is —N(R 2g ) 2 , —C(═O)(R 2g ), —C(═O)O(R 2g ), —C(═O)N(R 2g ) 2 , —N(R 2g )C(═O)(R 2g ), —S(═O) 2 (R 2g ), —S(O) 2 N(R 2g ) 2 , lower alkyl, lower alkoxy, lower haloalkyl, phenyl, heteroaryl, heteroaryloxy, cycloalkyl, or heterocycloalkyl, optionally substituted with one or more R 2f ;

 each R 2f is independently H, halogen, lower alkyl, lower alkoxy, or lower haloalkyl;

 each R 2g is independently H, lower alkyl, lower alkoxy, lower haloalkyl, or phenyl;

R 3 is —C(═O)R 3a ;

R 3a is lower alkyl, lower alkoxy, phenyl, or N(R 3b ) 2 ;

each R 3b is independently H or lower alkyl;

R 4 is —O(R 4a );

R 4a is H or R 4b ;

R 4b is lower alkyl, phenyl, benzyl, lower haloalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, optionally substituted with one or more R 4c ;

R 4c is halogen, hydroxy, lower alkyl, lower haloalkyl, or lower alkoxy;

Q 3 is —O-Q 3a , —S-Q 3a , —C(═O)(Q 3a ), —S(═O)(Q 3a ), —S(═O) 2 (Q 3a ), —N(Q 3a ) 2 , —NHC(═O)(Q 3a ), —C(═O)N(Q 3a ) 2 , or —NHC(═O)N(Q 3a ) 2 ;

each Q 3a is independently Q 3b or Q 3c ;

Q 3b is H;

Q 3c is lower alkyl, lower haloalkyl, phenyl, cycloalkyl, heterocycloalkyl, or heteroaryl, optionally substituted with one or more Q 3d ; and

each Q 3d is independently Q 3e or Q 3f ;

Q 3e is halogen or hydroxy;

Q 3f is lower alkyl, lower alkoxy, or lower haloalkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R is R′.

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

4. The compound of claim 3 , wherein R 1 is tert-butyl.

5. The compound of claim 3 , wherein R 1 is —CHC(CH 3 ) 3 .

6. The compound of claim 3 , wherein R 1 is iso-butyl.

7. The compound of claim 3 , wherein R 1 is iso-propyl.

8. The compound of claim 2 , wherein R 1 is cycloalkyl.

9. The compound of claim 2 , wherein R 1 is heterocycloalkyl.

10. The compound of claim 2 , wherein R 1 is benzyl.

11. The compound of claim 2 , wherein R 1 is phenyl.

12. The compound of claim 1 , wherein R is R 2 .

13. The compound of claim 12 , wherein R 2 is NH(R 2a ).

14. The compound of claim 13 , wherein R 2a is R 2b and R 2b is lower alkyl.

15. The compound of claim 14 , wherein R 2b is iso-propyl.

16. The compound of claim 13 , wherein R 2a is R 2b and R 2b is heterocycloalkyl.

17. The compound of claim 13 , wherein R 2a is R 2b and R 2b is cycloalkyl.

18. The compound of claim 13 , wherein R 2a is R 2b and R 2b is heterocycloalkyl alkylene.

19. The compound of claim 18 , wherein R 2b is pyrrolidinyl alkylene.

20. The compound of claim 18 , wherein R 2b is pyrrolidinyl methylene.

21. A compound selected from the group consisting of:

2-(Cyclopentyl-methyl-amino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide;

1-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-2,2-dimethyl-propan-1-one;

1-(2-Cyclopentyloxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

N-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-benzamide;

Cyclohexanecarboxylic acid [7-(2,2-dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-amide;

N-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-N-methyl-benzamide;

N-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-benzenesulfonamide;

N-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-N-methyl-benzenesulfonamide;

7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazine-2-carboxylic acid dimethylamide;

7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazine-2-carboxylic acid isopropylamide;

1-(2-Acetyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

1-(2-Isobutyryl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

2,2-Dimethyl-1-[2-(2-methyl-benzoyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one;

1-(2-Benzoyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazine-2-carboxylic acid cyclopentylamide;

2,2-Dimethyl-1-[2-(pyridine-4-carbonyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one;

2,2-Dimethyl-1-[2-(pyridine-3-carbonyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one;

1-(2-Cycloheptyloxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

1-(2-Cyclohexyloxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

1-(2-Isopropoxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

1-(2-Ethoxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

2,2-Dimethyl-1-[2-(2-morpholin-4-yl-2-oxo-ethoxy)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one;

1-[2-(1,2-Dimethyl-propoxy)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one;

1-(2-Isobutoxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

1-[2-(1-Benzyl-1H-[1,2,3]triazol-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one;

1-Cyclohexyl-3-[7-(2,2-dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea;

1-Cycloheptyl-3-[7-(2,2-dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea;

2,2-Dimethyl-1-[2-(methyl-phenyl-amino)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one;

1-(2-sec-Butoxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

2,2-Dimethyl-1-(2-phenylamino-5H-pyrrolo[2,3-b]pyrazin-7-yl)-propan-1-one;

1-(2-Cyclopentyloxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one;

1-[2-(Cyclopentyl-methyl-amino)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one;

2,2-Dimethyl-1-(2-phenoxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-propan-1-one;

2,2-Dimethyl-1-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-propan-1-one;

1-Cyclohexyl-3-[7-(2,2-dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea;

1-Cycloheptyl-3-[7-(2,2-dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea;

1-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-2,2-dimethyl-propan-1-one; and

1-[2-(6-Methoxy-pyridin-2-ylamino)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one.

22. A pharmaceutical composition comprising the compound of claim 1 , admixed with at least one pharmaceutically acceptable carrier, excipient or diluent.

23. A compound of Formula I

R is R 1 , R 2 , R 3 , or R 4 ;

R 1 is lower alkyl, lower alkoxy, phenyl, benzyl, heteroaryl, cycloalkyl, heterocycloalkyl, or cycloalkylalkyl, optionally substituted with one or more R 1a ;

R 1a is R 1b or R ic ;

R 1b is halogen, oxo, hydroxy, or —CN;

R 1c is —C(═O)O(R 1f ), —C(═O)CH 2 (R 1e ), —S(R 1f ), —S(O) 2 (R 1f ), or —S(═O) (R 1f ), lower alkyl, lower alkoxy, amino, amido, lower haloalkyl, phenyl, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkyloxy, or heterocycloalkyloxy optionally substituted with one or more R 1d ;

R 1d is H, halogen, hydroxy, lower alkyl, lower alkoxy, or lower haloalkyl;

R 1e is H, lower alkyl, lower alkoxy, —CN, lower haloalkyl, phenyl, heteroaryl, cycloalkyl, or heterocycloalkyl;

R 1f is H, lower alkyl, lower haloalkyl, phenyl, heteroaryl, cycloalkyl, or heterocycloalkyl;

R 2 is N(R 2a ) 2 ;

each R 2a is independently H or R 2b ;

each R 2b is independently lower alkyl, phenyl, heteroaryl, cycloalkyl, heterocycloalkyl, or heterocycloalkyl alkylene, optionally substituted with one or more R 2c ;

R 2c is R 2d or R 2e ;

 R 2d is halogen, oxo, or hydroxy;

 R 2e is —N(R 2g ) 2 , —C(═O)(R 2g ), —C(═O)O(R 2g ), —C(═O)N(R 2g ) 2 , —N(R 2g )C(═O)(R 2g ), —S(═O) 2 (R 2g ), —S(O) 2 N(R 2g ) 2 , lower alkyl, lower alkoxy, lower haloalkyl, phenyl, heteroaryl, heteroaryloxy, cycloalkyl, or heterocycloalkyl, optionally substituted with one or more R 2f ;

 each R 2f is independently H, halogen, lower alkyl, lower alkoxy, or lower haloalkyl;

 each R 2g is independently H, lower alkyl, lower alkoxy, lower haloalkyl, or phenyl;

R 3 is —C(═O)R 3a ;

R 3a is lower alkyl, lower alkoxy, phenyl, or N(R 3b ) 2 ;

each R 3b is independently H or lower alkyl;

R 4 is —O(R 4a );

R 4a is H or R 4b ;

R 4b is lower alkyl, phenyl, benzyl, lower haloalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, optionally substituted with one or more R 4c ;

R 4c is halogen, hydroxy, lower alkyl, lower haloalkyl, or lower alkoxy;

Q 3 is —O-Q 3a , —S-Q 3a , —C(═O)(Q 3a ), —O(CH 2 ) m C(═O)(Q 3a ), —S(═O)(Q 3a ), —S(═O) 2 (Q 3a ), —N(Q 3a ) 2 , —N(Q 3a )S(═O) 2 (Q 3a ), —N(Q 3a )C(═O)(Q 3a ), —C(═O)N(Q 3a ) 2 , or —N(Q 3a )C(═O)N(Q 3a ) 2 ;

each Q 3a is independently Q 3b or Q 3c ;

m is 0, 1, or 2;

Q 3b is H;

Q 3c is lower alkyl, lower haloalkyl, phenyl, heterocycloalkyl, or heteroaryl, optionally substituted with one or more Q 3d ; and

each Q 3d is independently Q 3e or Q 3f ;

Q 3e is halogen or hydroxy;

Q 3f is lower alkyl, lower alkoxy, lower haloalkyl, phenyl, cycloalkyl, heterocycloalkyl, or heteroaryl, optionally substituted with one or more Q 3g ; and

each Q 3g is independently halogen, hydroxy, lower alkyl, lower hydroxyalkyl, lower haloalkyl, or lower alkoxy;

or a pharmaceutically acceptable salt thereof.