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

摘要

Benzimidazole derivatives (I) their enantiomers and diastereoisomers and racemic mixtures, and their salts are new. Benzimidazole derivatives (I) their enantiomers and diastereoisomers, their racemic 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; R4 = H, 1-6C alkyl, 3-7C cycloalkyl, benzyl (optionally substituted on the phenyl ring by halogen, CF3, 1-4C alkyl or alkoxy, or NO2), phenyl ethyl, pyridyl, aminopyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, or imidazolyl, 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), phenyl (optionally substituted by 1-3 groups selected from halogen, CF3, 1-4C alkyl or alkoxy, NO2, NH2, mono- and di-alkylamino, -NHCHO, NHCOR'); p = 0 - 4; R = 1-6C alkyl; R' = 1-4C alkyl or alkoxy, the alkyl being optionally substituted by dimethylamino; 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, a group -(CH2)t-NR7R8; R5, R6 = H or 1-4C alkyl; R7, R8 = 1-4C alkyl 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 with the proviso that when X = C and R4 = -NR7R8, then R3 is other than -NR5R6, -NHCOR7 , -NHCONH2, and OH. An Independent claim is included for an intermediate of formula (II) A = a leaving group