| 摘要 |
Tricyclic 2-(cyclic amino)-benzimidazole derivatives (I) are new. Also new are intermediates (II). Benzimidazole derivatives for formula (I), in the form of enantiomers, diastereomers or their mixtures (including racemic mixtures), and their acid addition salts are new. R1 = H, T, halo, NO2 or OT; T = 1-4C alkyl; R2, R'2 = H or T; X = NR3R4 or CR'3R'4; n, m = 1 or 2; R3 = H or T (giving a quaternary ammonium structure); or is absent; R4 = H, R, 3-7C cycloalkyl, 3-7C heterocycloalkyl (optionally substituted (os) by T or COOR), -(CH2)p-Het1, -COHet2, benzoyl (os by halo), -(CH2)pCOOR, phenylsulfonyl (os by halo, CF3, T, NO2 or OT) or -(CH2)p-Ph'; R = 1-6C alkyl; p = 0-4; Het1 = pyridyl, aminopyridyl, pyrazinyl, pyridazinyl, imidazolyl or thienyl (all os by T); Het2 = furyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl or imidazolyl; Ph' = phenyl (os by 1-3 of T, NO2, NH2, OH, halo, CF3, OT, (1-4C) alkoxyphenyl, NHT, NT2, NHCHO or NHCOR'; R' = OT or T (os by NMe2); R'3 = H, NR5R6, N<+>(R5)3, NHCOR7, CONHR5, COR7, NHCONH2, OH or CH2OH; R'4 = H, -(CH2)p-Ph (os in the ring by 1-3 of T, NO2, NH2, halo, CF3 or OT), -(CH2)p-Het3, -(CH2)NR7R8 or -NR7R8 (provided that if R'4 = NR7R8, then R'3 is other than NR5R6, NHCOR7, NHCONH2 or OH); R5, R6 = H or T; R7, R8 = T or OT; or NR7R8 = 5-7 membered saturated ring, os on C or N (including the N to which R7 and R8 are bonded, giving a quaternary ammonium structure) by T or COOR''; Het3 = imidazolyl (os by T), pyridyl, aminopyridyl, pyrimidyl, pyrazinyl or pyridazinyl; R'' = phenyl or (1-4C) alkylphenyl; provided that compounds (I; R1, R2, R2' = H; m, n = 1; X = CHR'4; R'4 = imidazol-4-yl or 5-methyl-imidazol-4-yl), i.e. (I'), are excluded. Independent claims are included for: (i) preparation of (I); (ii) new benzimidazole derivative intermediates of formula (II); (iii) and (iii) the use of (I), including (I'), for preparing a medicament for treating or preventing disorders involving the enzyme poly-(ADP-ribose) polymerase (PARP). A = leaving group. |
