Benzimidazole poly(adp ribose)polymerase inhibitors

Abstract

Compounds which inhibit the activity of poly(ADP-ribose)polymerase (PARP), compositions containing the compounds and methods of treating diseases using them are disclosed.

We claim: 
     
         1 - 17 . (canceled) 
     
     
         18 . A compound of Formula III: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein
 A 1  is heteroaryl which is substituted with A 2  and unfused; 
 A 2  is is heteroaryl; 
 wherein A 2  is 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. 
 
     
     
         19 . The compound of  claim 18 , wherein A 1  is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         20 . The compound of  claim 18 , wherein A 2  is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         21 . The compound of  claim 20 , wherein A 2  is unsubstituted. 
     
     
         22 . The compound of  claim 20 , wherein A 2  is substituted with R 10 , R 11 , or CF 3 . 
     
     
         23 . The compound of  claim 22 , wherein A 2  is substituted with cycloalkyl, heterocycloalkyl, alkyl, or CF 3 . 
     
     
         24 . The compound of  claim 18  which is
 2-(4-pyridin-3-yl-1,3-thiazol-2-yl)-1H-benzimidazole-4-carboxamide, 
 2-(4-pyridin-4-yl-1,3-thiazol-2-yl)-1H-benzimidazole-4-carboxamide, 
 2-(4-methyl-2-pyrazin-2-yl-1,3-thiazol-5-yl)-1H-benzimidazole-4-carboxamide, 
 2-(2-thien-2-yl-1,3-thiazol-4-yl)-1H-benzimidazole-4-carboxamide, 
 2-(5-pyridin-2-ylthien-2-yl)-1H-benzimidazole-4-carboxamide, 
 2-(5-pyrazin-2-ylthien-2-yl)-1H-benzimidazole-4-carboxamide, 
 2-(5-pyrimidin-2-ylthien-2-yl)-1H-benzimidazole-4-carboxamide, 
 2-(5-pyridin-3-ylthien-2-yl)-1H-benzimidazole-4-carboxamide, 
 2-(5-pyridin-4-ylthien-2-yl)-1H-benzimidazole-4-carboxamide, 
 2-(5-(1H-pyrrol-2-yl)thien-2-yl)-1H-benzimidazole-4-carboxamide, 
 2-[6-(1,3-oxazol-5-yl)pyridin-3-yl]-1H-benzimidazole-4-carboxamide; 
 2-[5-(1,3,4-oxadiazol-2-yl)pyridin-2-yl]-1H-benzimidazole-4-carboxamide; 
 2-{5-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl}-1H-benzimidazole-4-carboxamide; 
 2-[5-(5-methyl-1,3,4-oxadiazol-2-yl)pyridin-2-yl]-1H-benzimidazole-4-carboxamide; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         25 . A pharmaceutical composition comprising a compound of claim  17  and pharmaceutically acceptable excipient.