Benzimidazole poly(ADP ribose)polymerase inhibitors

1. A compound of Formula I

or a salt thereof, wherein

A 1 is heteroaryl which is substituted with A 2 and unfused;

A 2 is

B 1 is hydrogen or R 3 ;

R 3 is alkyl;

C 1 , D 1 , E 1 are each independently hydrogen, NO 2 , CN, R 5 , OR 5 , CO(O)R 5 , C(O)NH 2 , C(O)NHR 5 , C(O)N(R 5 ) 2 , NH 2 , NHR 5 , N(R 5 ) 2 , OH F, Cl, Br or I;

R 5 is alkyl, alkenyl or alkynyl; each of which is unsubstituted or substituted with one or two substituents independently selected from R 6 , NH 2 , NHR 6 , N(R 6 ) 2 , C(O)NH 2 , C(O)NHR 6 , C(O)N(R 6 ) 2 , OH, F, Cl, Br and I;

R 6 is alkyl or cycloalkyl;

wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two or three or four or five substituents independently selected from R 7 , OR 7 , SR 7 , S(O)R 7 , SO 2 R 7 , C(O)R 7 , CO(O)R 7 , OC(O)R 7 , OC(O)OR 7 , NO 2 , NH 2 , NHR 7 , N(R 7 ) 2 , CH 2 R 7 , C(O)NH 2 , C(O)NHR 7 , C(O)N(R 7 ) 2 , C(O)NHOH, C(O)NHOR 7 , C(O)NHSO 2 R 7 , C(O)NR 7 SO 2 R 7 , SO 2 NH 2 , SO 2 NHR 7 , SO 2 N(R 7 ) 2 , CF 3 , CF 2 CF 3 , C(O)H, C(O)OH, C(N)NH 2 , C(N)NHR 7 , C(N)N(R 7 ) 2 , CNOH, CNOCH 3 , OH, (O), N 3 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, Cl, Br and I;

R 7 is R 8 , R 9 , R 10 or R 11 ;

R 8 is phenyl each of which is unfused or fused with benzene, heteroarene or R 8A ; R 8A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 9 is heteroaryl which is unfused or fused with benzene, heteroarene or R 9A ; R 9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 10 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 10A ; R 10A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 11 is alkyl, alkenyl, or alkenyl, each of which is unsubstituted or substituted with one, two, three, four or five substituents independently selected from R 12 , OR 12 , SR 12 , S(O)R 12 , SO 2 R 12 , NH 2 , NHR 12 , N(R 12 ) 2 , C(O)R 12 , C(O)NH 2 , C(O)NHR 12 , C(O)N(R 12 ) 2 , NHC(O)R 12 , NR 12 C(O)R 12 , NHSO 2 R 12 , NR 12 SO 2 R 12 , NHC(O)OR 12 , NR 12 C(O)OR 12 , SO 2 NH 2 , SO 2 NHR 12 , SO 2 N(R 12 ) 2 , NHC(O)NH 2 , NHC(O)R 12 NHC(O)N(R 12 ) 2 , NR 12 C(O)N(R 12 ) 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br and I;

R 12 is R 13 , R 14 , R 15 or R 16 ;

R 13 is phenyl which is unfused or fused with benzene, heteroarene or R 13A ; R 13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 14 is heteroaryl which is unfused or fused with benzene, heteroarene or R 14A ; R 14A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 15 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 15A ; R 15A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 16 is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with R 17 ; and

R 17 is phenyl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycloalkyl.

2. A compound of claim 1 , wherein C 1 , D 1 , and E 1 are hydrogen.

3. A compound of claim 2 , wherein B 1 is hydrogen.

4. A compound of claim 3 , wherein A 1 is selected from the group consisting of

wherein each A 1 is substituted with A 2 .

5. A compound of claim 4 , wherein A 2 is unsubstituted or substituted with R 7 or CF 3 .

6. A compound of claim 4 , wherein A 2 is unsubstituted or substituted with R 10 , R 11 or CF 3 .

7. A compound of claim 4 , wherein A 2 is unsubstituted or substituted with cycloalkyl, heterocycloalkyl, alkyl, or CF 3 .

8. A compound of claim 4 , wherein A 2 is unsubstituted or substituted with cycloalkyl, heterocycloalkyl, alkyl, or CF 3 —; wherein the alkyl is unsubstituted or substituted with R 12 ; R 12 is R 14 or R 15 ; R 14 is heteroaryl which is unfused; and R 15 is cycloalkyl, which is unfused.

9. A compound of claim 8 which is

2-(2-piperidin-4-yl-1,3-thiazol-4-yl)-1H-1-benzimidazole-4-carboxamide,

2-(2-(1-methylpiperidin-4-yl)-1,3-thiazol-4-yl)-1H-benzimidazole-4-carboxamide,

2-(2-(1-isopropylpiperidin-4-yl)-1,3-thiazol-4-yl)-1H-benzimidazole-4-carboxamide,

2-(2-(1-propylpiperidin-4-yl)-1,3-thiazol-4-yl)-1H-benzimidazole-4-carboxamide,

2-(2-(1-cyclobutylpiperidin-4-yl)-1,3-thiazol-4-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-pyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-methylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-isopropylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-propylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-(cyclopropylmethyl)pyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-cyclobutylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-cyclopentylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-cyclohexylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-tetrahydro-2H-pyran-4-ylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-(pyridin-2-ylmethyl)pyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-(pyridin-4-ylmethyl)pyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-((2R)-1-isobutylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-piperidin-2-ylthien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-methylpiperidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-propylpiperidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-(cyclopropylmethyl)piperidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-cyclobutylpiperidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-isobutylpiperidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-pyrrolidin-2-ylthien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-methylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-isopropylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-propylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-(cyclopropylmethyl)pyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-isobutylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-cyclobutylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-cyclopentylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(5-(1-cyclohexylpyrrolidin-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide,

2-(6-pyrrolidin-2-ylpyridin-3-yl)-1H-benzimidazole-4-carboxamide;

2-[6-(1-isopropylpyrrolidin-2-yl)pyridin-3-yl]-1H-benzimidazole-4-carboxamide;

2-[6-(1-isobutylpyrrolidin-2-yl)pyridin-3-yl]-1H-benzimidazole-4-carboxamide;

2-[6-(1-cyclobutylpyrrolidin-2-yl)pyridin-3-yl]-1H-benzimidazole-4-carboxamide;

2-[6-(1-cyclopentylpyrrolidin-2-yl)pyridin-3-yl]-1H-benzimidazole-4-carboxamide;

2-[6-(1-cyclohexylpyrrolidin-2-yl)pyridin-3-yl]-1H-benzimidazole-4-carboxamide; or

2-[6-(1-tetrahydro-2H-pyran-4-ylpyrrolidin-2-yl)pyridin-3-yl]-1H-benzimidazole-4-carboxamide;

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound of claim 1 and pharmaceutically acceptable excipient.