Benzimidazole derivatives, preparation and therapeutic use thereof

A method for the treatment of disorders in which the enzyme poly (ADP-ribose) polymerase is involved which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound having formula (I)

• in which:
• R1 represents a hydrogen atom, a C1-C4 alkyl group, a halogen atom, a nitro group or a C1-C4 alkoxy group,
• R2 and R2′ represent, independently of each other, a hydrogen atom or a C1-C4 alkyl group,
• X represents a nitrogen atom or a carbon atom,
• n is equal to 1 or 2,
• m is equal to 1 or 2,
• and, when X represents a nitrogen atom:
• R3 is not present or represents a C1-C4 alkyl group, and
• R4 represents
• a hydrogen atom,
• a C1-C6 alkyl group,
• a C3-C7 cycloalkyl group,
• a C3-C7 heterocycloalkyl group optionally substituted with a C1-C4 alkyl group or a group —COOR, in which R represents a C1-C6 alkyl group,
• a group —(CH2)p-heteroaryl, in which p may range from 0 to 4 and in which the heteroaryl group is chosen from pyridyl, aminopyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl and thienyl groups, the said heteroaryl group optionally being substituted with a C1-C4 alkyl group,
• a heteroarylcarbonyl group, the heteroaryl group being chosen from furyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl and imidazolyl groups,
• a phenylcarbonyl group, the phenyl group optionally being substituted with a halogen atom,
• a (C1-C6)alkylcarbonyl group,
• a group —(CH2)pCOOR in which p may range from 0 to 4 and in which R represents a C1-C6 alkyl group,
• a phenylsulphonyl group optionally substituted on the phenyl nucleus with a halogen atom, a trifluoromethyl group, a C1-C4 alkyl group, a nitro group or a C1-C4 alkoxy group, or
• a —(CH2)p-phenyl group, in which p may range from 0 to 4 and in which the phenyl group is optionally substituted with one to three groups chosen, independently of each other, from:
• a C1-C4 alkyl group, a nitro group, an amino group, a hydroxyl group, a halogen atom, a trifluoromethyl group, a C1-C4 alkoxy group, a (C1-C4)alkoxyphenyl group, a C1-C4 alkylamino group, a C1-C4 dialkylamino group, an —NHCHO group or a group —NHCOR′, in which R′ represents a C1-C4 alkoxy group or a C1-C4 alkyl group, this C1-C4 alkyl group optionally being substituted with a dimethylamino group,
• and, when X represents a carbon atom:
• R3 represents a hydrogen atom, a group —NR5R6, a group —N(R5)3+, a group —NHCOR7, a group —CONHR5, a group —COR7, an —NHCONH2 group, an —OH group or a —CH2OH group,
• R4 represents
• a hydrogen atom,
• a —(CH2)p-phenyl group, in which p may range from 0 to 4 and in which the phenyl group is optionally substituted with one to three groups chosen, independently of each other, from:
• a C1-C4 alkyl group, a nitro group, an amino group, a halogen atom, a trifluoromethyl group or a C1-C4 alkoxy group,
• a —(CH2)p-heteroaryl group, in which p may range from 0 to 4 and in which the heteroaryl group is chosen from an imidazolyl group, optionally substituted with a C1-C4 alkyl group, a pyridyl group, an aminopyridyl group, a pyrimidinyl group, a pyrazinyl group or a pyridazinyl group, or
• a group —(CH2)tNR7R8, in which t is equal to 0 or 1,
• R5 and R6 represent, independently of each other, a hydrogen atom or a C1-C4 alkyl group, and
• R7 and R8 represent, independently of each other, a C1-C4 alkyl or C1-C4 alkoxy group or together form a saturated 5- to 7-membered ring optionally comprising an additional nitrogen atom, this ring optionally being substituted, on a carbon atom or on a nitrogen atom, including the nitrogen atom to which the groups R7 and R8 are attached, with a C1-C4 alkyl group or a group —COOR″, in which R″ represents a phenyl or (C1-C4)alkylphenyl group,
• or a pharmaceutically acceptable acid addition salt thereof,
• with the proviso that when R4 represents a group —NR7R8, R3 is other than —NR5R6, —NHCOR7, —NHCONH2 or —OH, and when R1=R2=R2′=R3=H, X=C and n=m=1, R4 is other than 4-imidazolyl or 5-methyl-4-imidazolyl.