Benzimidazole compounds

A compound having the structural formula I

• or a pharmaceutically acceptable salt thereof,
• wherein
• R is selected from the group consisting of hydrogen, hydroxyalkyl and a phenyl group which is substituted by one or more substituents in the benzene ring selected from the group consisting of NO2, N3, NHCOR3 (R3 being alkyl or aryl), CO2R4 (R4 being H or alkyl), an amide, tetrazole, alkyl, hydroxylalkyl, CW3 or W (W being halogen), and CN R′ is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, acyl and an optionally substituted phenyl group having the structural formula III
• wherein R7, R8 and R10 are each selected independently from the group consisting of H, hydroxy, alkoxy, NO2, N3, NR5R6 (R5 and R6 each being independently hydrogen, alkyl or alkoxy), NHCOR3 (R3 being alkyl or aryl), CO2R4 (R4 being H or alkyl), an amide, tetrazole, alkyl, hydroxylalkyl, CW3 or W (W being halogen), and CN.

A benzimidazole compound which is one of the following:

• 2-(4′-trifluoromethylphenyl)benzimidazole-4-carboxamide;
• 2-(4′-nitrophenyl)benzimidazole-4-carboxamide;
• 2-(4′-cyanophenyl)benzimidazole-4-carboxamide;
• 2-(3′-trifluoromethylphenyl)benzimidazole-4-carboxamide;
• or
• 2-(2′-trifluoromethylphenyl)benzimidazole-4-carboxamide.

A pharmaceutical composition comprising an effective poly(ADP-ribose)polymerase or PARP enzyme inhibiting amount of a benzimidazole compound having the structural formula I

• or a pharmaceutically acceptable salt and/or pro-drug form thereof, together with a pharmaceutically acceptable carrier,
• wherein
• R is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and benzyl and phenyl groups which are unsubstituted or substituted with at least one substituent in the benzene ring selected from the group consisting of hydroxy, alkoxy, NO2, N3, NR5R6 (R5 and R6 each being independently hydrogen, alkyl or alkoxy), NHCOR3 (R3 being alkyl or aryl), CO2R4 (R4 being H or alkyl), an amide, tetrazole, alkyl, hydroxyalkyl, CW3 or W (W being halogen), and CN, and
• R′ is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, acyl and an optionally substituted phenyl group having the structural formula III:
• wherein R7, R8 and R10 are each selected independently from the group consisting of H, hydroxy, alkoxy, NO2, N3, NR5R6 (R5 and R6 each being independently hydrogen, alkyl or alkoxy), NHCOR3 (R3 being alkyl or aryl), CO2R4 (R4 being H or alkyl), an amide, tetrazole, alkyl, hydroxyalkyl, CW3 or W (W being halogen), carboxybenzyl, and CN,
• said pharmaceutical composition being in the form of a sterile liquid preparation for parenteral use.

A pharmaceutical composition comprising a solution in phosphate buffered saline of an effective and non-toxic poly(ADP-ribose)polymerase or PARP enzyme inhibiting amount of a benzimidazole compound having the structural formula I

• or of a pharmaceutically acceptable salt and/or pro-drug form thereof,
• wherein
• R is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and benzyl and phenyl groups which are unsubstituted or substituted with one or more substituents in the benzene ring selected from the group consisting of hydroxy, alkoxy, NO2, N3, NR5R6 (R5 and R6 each being independently hydrogen, alkyl or alkoxy), NHCOR3 (R3 being alkyl or aryl), CO2R4 (R4 being H or alkyl), an amide, tetrazole, alkyl, hydroxyalkyl, CW3 or W (W being halogen), and CN, and
• R′ is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, acyl and an optionally substituted phenyl group having the structural formula III:
• wherein R7, R8 and R10 are each selected independently from the group consisting of H, hydroxy, alkoxy, NO2, N3, NR5R6 (R5 and R6 each being independently hydrogen, alkyl or alkoxy), NHCOR3 (R3 being alkyl or aryl), CO2R4 (R4 being H or alkyl), an amide, tetrazole, alkyl, hydroxyalkyl, CW3 or W (W being halogen), carboxybenzyl, and CN.