Substituted pyrazines as kinase inhibitors

1. A compound of formula (I)

wherein:

D is a heterocyclic ring selected from:

where X 1 , X 2 , X 3 , X 4 are optionally substituted carbon, or one of X 1 , X 2 , X 3 , X 4 is nitrogen and the rest optionally substituted carbon;

R 2 is 0-3 substituents independently selected from the group consisting of halogen, C 1-4 alkyl, CF 3 , OCF 3 , OCHF 2 , CN, aryl, hetaryl, C 1-4 alkylOH, C 1-4 alkylNR 3 R 4 , C 1-4 alkylhetaryl, OC 1-4 alkyl, OC 1-4 alkylNR 3 R 4 , OC 1-4 alkylhetaryl, OC 1-4 alkylOH, CO 2 R 3 , CONR 3 R 4 , NR 3 R 4 , nitro, NR 3 COR 4 , NR 5 CONR 3 R 4 , NR 3 SO 2 R 4 , C 1-4 alkylNR 3 COR 4 , C 1-4 alkylNR 5 CONR 3 R 4 and C 1-4 alkylNR 3 SO 2 R 4 ;

R 3 and R 4 are each independently H, C 1-4 alkyl, C 1-4 alkylOH, C 1-4 alkylNR 19 R 20 , C 1-4 alkyl cycloalkyl, C 3-8 cyclohetalkyl, aryl, C 1-4 alkylaryl, hetaryl, or C 1-4 alkylhetaryl, or may be joined to form an optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S and NR 6 ;

and R 5 is H, C 1-4 alkyl, aryl or hetaryl;

R 6 is selected from the group consisting of H, C 1-4 alkyl, C 1-4 alkylNR 19 R 20 , aryl, hetaryl, C 1-4 alkyl aryl and C 1-4 alkyl hetaryl;

R 19 and R 20 are each independently H or C 1-4 alkyl;

R 1 is H, C 1-4 alkyl, C 3-6 cycloalkyl, or may form a 5-8 membered ring onto the ortho position of ring A;

A is aryl or hetaryl optionally substituted with 0-3 substituents independently selected from the group consisting of halogen, C 1-4 alkyl, CF 3 , OCF 3 , CN, NR 8 R 9 , aryl, hetaryl, C 1-4 alkylNR 8 R 9 , OC 1-4 alkylNR 8 R 9 , nitro, NR 10 C 1-4 NR 8 R 9 , NR 8 COR 9 , NR 10 CONR 8 R 9 , NR 8 SO 2 R 9 , CONR 8 R 9 and CO 2 R 8 ;

R 8 and R 9 are each independently H, C 1-4 alkyl, aryl or together form an optionally substituted 4-8 membered ring which may contain a heteroatom selected from O, S and NR 11 ;

R 10 is H or C 1-4 alkyl;

R 11 is H or C 1-4 alkyl; and

either Q is C 1-4 alkylene; and W is H, C 1-4 alkyl, or C 2-6 alkenyl or may form a 5-8 membered ring onto the ortho position of ring A; where C 1-4 alkyl or C 2-6 alkenyl may be optionally substituted with C 1-4 alkyl, OH, OC 1-4 alkyl or NR 12 R 13 ; R 12 and R 13 are each independently H, C 1-4 alkyl, or may be joined to form an optionally substituted 3-8 membered ring optionally containing an atom selected from O, S and NR 14 ; R 14 is H or C 1-4 alkyl; or

Q and W are absent;

Y is 0-2 substituents selected from H, C 1-4 alkyl, NR 15 R 16 ;

R 15 and R 16 are independently H or C 1-4 alkyl; and pharmaceutically acceptable salts or diastereomers thereof; or

a compound selected from a group consisting of:

and pharmaceutically acceptable salts, or diastereomers thereof; or

a compound selected from:

or a pharmaceutically acceptable salt, or diastereomer thereof.

2. A compound according to formula (I) of claim 1 , wherein the compound is of formula (II):

wherein:

D is a heterocyclic ring of the formula:

where X 1 , X 2 , X 3 , X 4 are optionally substituted carbon, or one of X 1 , X 2 , X 3 , X 4 is N and the rest optionally substituted carbon;

R 2 is 0-3 substituents independently selected from the group consisting of halogen, C 1-4 alkyl, CF 3 , OCF 3 , OCHF 2 , CN, aryl, hetaryl, C 1-4 alkylOH, C 1-4 alkylNR 3 R 4 , C 1-4 alkylhetaryl, OC 1-4 alkyl, OC 1-4 alkylNR 3 R 4 , OC 1-4 alkylhetaryl, OC 1-4 alkylOH, CO 2 R 3 , CONR 3 R 4 , NR 3 R 4 , nitro, NR 3 COR 4 , NR 5 CONR 3 R 4 , NR 3 SO 2 R 4 , C 1-4 alkylNR 3 COR 4 , C 1-4 alkylNR 5 CONR 3 R 4 and C 1-4 alkylNR 3 SO 2 R 4 ;

R 3 and R 4 are each independently H, C 1-4 alkyl, C 1-4 alkylOH, C 1-4 alkylNR 19 R 20 , C 1-4 alkyl cycloalkyl, C 3-8 cyclohetalkyl, aryl, C 1-4 alkylaryl, hetaryl, or C 1-4 alkylhetaryl, or may be joined to form an optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S and NR 6 ;

and R 5 is H, C 1-4 alkyl, aryl or hetaryl;

R 6 is selected from the group consisting of H, C 1-4 alkyl, C 1-4 alkylNR 19 R 20 , aryl, hetaryl, C 1-4 alkyl aryl, and C 1-4 alkyl hetaryl;

R 19 and R 20 are each independently H or C 1-4 alkyl;

R 1 is H, C 1-4 alkyl, C 3-6 cycloalkyl, or may form a 5-8 membered ring onto the ortho position of ring A;

A is aryl, or hetaryl optionally substituted with 0-3 substituents independently selected from the group consisting of halogen, C 1-4 alkyl, CF 3 , OCF 3 , CN, NR 8 R 9 , aryl, hetaryl, C 1-4 alkylNR 8 R 9 , OC 1-4 alkylNR 8 R 9 , nitro, NR 10 C 1-4 NR 8 R 9 , NR 8 COR 9 , NR 10 CONR 8 R 9 , NR 8 SO 2 R 9 , CONR 8 R 9 and CO 2 R 8 ;

R 8 and R 9 are each independently H, C 1-4 alkyl, aryl or together form an optionally substituted 4-8 membered ring which may contain a heteroatom selected from O, S and NR 11 ;

R 10 is H or C 1-4 alkyl;

R 11 is H or C 1-4 alkyl;

W is selected from the group consisting of H, C 1-4 alkyl, and C 2-6 alkenyl or may form a 5-8 membered ring onto the ortho position of ring A; where C 1-4 alkyl or C 2-6 alkenyl may be optionally substituted with C 1-4 alkyl, OH, OC 1-4 alkyl and NR 12 R 13 ;

R 12 and R 13 are each independently H, C 1-4 alkyl, or may be joined to form an optionally substituted 3-8 membered ring optionally containing an atom selected from O, S and NR 14 ;

R 14 is H or C 1-4 alkyl;

Y is 0-2 substituents selected from the group consisting of H, C 1-4 alkyl and NR 15 R 16 ;

R 15 and R 16 are independently H or C 1-4 alkyl; or

a pharmaceutically acceptable salt, or diastereomer thereof.

3. A compound selected from the group consisting of:

or pharmaceutically acceptable salts, or diastereomers thereof.

4. A compound selected from the group consisting of

6-(1H-Benzimidazol-1-yl)-N-benzylpyrazin-2-amine,

6-(1H-Benzimidazol-1-yl)-N-[(1R)-1-phenylethyl]pyrazin-2-amine,

6-(1H-Benzimidazol-1-yl)-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

1-(6-{[1-(3-Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazole-5-carboxamide,

1-(6-{[1-(3-Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazole-6-carboxamide,

1-(6-{[1-(3-Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazole-6-carbonitrile,

1-[6-(3,4-Dihydroisoquinolin-2(1H)-yl)pyrazin-2-yl]-1H-benzimidazole-5-carbonitrile,

1-[6-(3,4-Dihydroisoquinolin-2(1H)-yl)pyrazin-2-yl]-1H-benzimidazole-6-carbonitrile,

1-{6-[(1S)-1,2,3,4-Tetrahydronaphthalen-1-ylamino]pyrazin-2-yl}-1H-benzimidazole-5-carbonitrile,

1-{6-[(1S)-1,2,3,4-Tetrahydronaphthalen-1-ylamino]pyrazin-2-yl}-1H-benzimidazole-6-carbonitrile,

1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-amine,

1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-amine,

N-[1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]-2,2-dimethylpropanamide,

N-[1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]acetamide,

N-[1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]methanesulfonamide,

2-(S-α-Methylbenzylamino)-6-(5-(N-methylpiperazin-4-yl-methyl)-benzimidazo-1-yl)-pyrazine,

[1-(6-{[1-(4-Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]methanol,

[1-(6-{[1-(4-Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]methanol, and

N-[1-(4-Fluorophenyl)ethyl]-6-{6-[(4-methylpiperazin-1-yl)methyl]-1H-benzimidazol-1-yl}pyrazin-2-amine, and

a pharmaceutically acceptable salt, or diastereomer thereof.

5. The compound of claim 1 , wherein said compound is:

or a pharmaceutically acceptable salt, or diastereomer thereof.

6. A composition comprising a carrier and at least one compound according to claim 1 .

7. The compound of claim 1 , wherein Y is 1-2 substituents.

8. The compound of claim 1 , wherein Y is 0 substituents and R 2 is OCHF 2 , CN, C 1-4 alkylOH, C 1-4 alkylhetaryl, OC 1-4 alkyl, OC 1-4 alkylNR 3 R 4 , OC 1-4 alkylhetaryl, or OC 1-4 alkylOH.

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

10. The compound of claim 1 , wherein R 1 forms a 5-8 membered ring onto the ortho position of ring A.

11. The compound of claim 10 , wherein Q is CH and W is H.

12. A compound selected from a group consisting of:

or a pharmaceutically acceptable salt, or diastereomer thereof.