Benzimidazole derivatives having poly(ADP-ribose) polymerase inhibiting activity for treatment of cardiac, cerebral, inflammatory, immunological and other disorders

摘要

Benzimidazole derivatives (I) their enantiomers and diastereoisomers and mixtures, and their salts are new. Benzimidazole derivatives (I) their enantiomers and diastereoisomers, their mixtures, and their salts are new. R1 = H, 1-4C alkyl or alkoxy, halogen, or NO2; R2, R2' = H or 1-4C alkyl; X = N or C; m = 1 or 2; when X is N, then R3 = H, 1-4C alkyl, or it does not exist; R4 = H, 1-6C alkyl, 3-7C cycloalkyl, 4-piperidiyl, (optionally substituted on N or C 1-4C alkyl), -(CH2)p-CONR5R6, -CH2-phenyl (the phenyl being optionally substituted by 1-3 of the following: 1-4C alkyl, NO2, NH2, halogen, CF3, 1-4C alkoxy, 1-4C alkylamino, 1-4C dialkylamino, NHCHO, or NHCOR), -(CH2)p-morpholinyl, -(CH2)p-pyrrolidinyl, -(CH2)p-tetrahydroisoquinoline, -(CH2)p-heteroaryl (the heteroaryl being pyridyl, aminopyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl or pyrazolyl, and being optionally substituted on N or C by 1-3 alkyl or phenyl groups), furyl carbonyl, pyridyl carbonyl, pyrimidinyl carbonyl, pyrazinyl carbonyl, pyridazinyl carbonyl, or imidazolyl carbonyl, phenyl carbonyl (optionally substituted by halogen), 1-6C alkyl carbonyl, -(CH2)p-COOR', phenyl sulfonyl (optionally substituted by halogen, CF3, 1-4C alkyl or alkoxy, or NO2); p = 0 - 4; R = 1-4C alkyl optionally substituted by dimethylamino, or 1-4C alkoxy; R' = H or 1-6C alkyl; R5, R6 = H or 1-4C alkyl; when X is C, then R3 = H, -NR5R6, -NHCOR7, -CONHR5, -COR7, -NHCONH2, OH, or -CH2OH; R4 = H, phenyl (optionally substituted by 1-3 groups selected from halogen, CF3, 1-4C alkyl or alkoxy, NO2, or NH2), imidazolyl optionally substituted by 1-4C alkyl, pyridyl, aminopyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl (optionally substituted on N or C by phenyl that may itself be substituted by 1-3 halogens or alkyl groups), a group -(CH2)t-NR7R8; R5, R6 = H or 1-4C alkyl; R7, R8 = 1-4C alkyl or alkoxy or together form a 5-7 membered ring that contain a further N atom and may be substituted by 1-4C alkyl and may be in the form or a quaternary ammonium sa t = 0 or 1 An Independent claim is included for an intermediate of formula (II). A = a leaving group