| 摘要 |
Benzimidazolyl-substituted (hetero)aromatic amidine or nitrile derivatives (I) are new. Benzimidazoles of formula (I) and their tautomers, stereoisomers, mixtures, prodrugs, derivatives (having a group which is negatively charged instead of COOH) and salts are new. Ar = phenylene or naphthylene (both optionally substituted by F, Cl, Br, CF3, T or OT); or thienylene, thiazolylene, pyridinylene, pyrimidinylene, pyrazinylene or pyridazinylene (all optionally substituted on C by T); T = 1-3C alkyl; A = 1-3C alkylene; B' = O, S, CF2, CO, SO, SO2, NH or NT (optionally substituted on T by 1 or 2 of COOH); Ra = R1-CO-(3-5C) cycloalkylene; R2-C(X)-(3-5C) cycloalkylene; T or 3-5C cycloalkyl, (both substituted by (a) imidazolyl, optionally substituted by one Ph or COOH and 1 or 2 T or by 1-3 T, where T moieties are optionally substituted by COOH or in the 2- or 3-position by NH2, NHCOT, NHT, N(T)COT or N(T)2, (b) imidazolonyl, optionally substituted by T (optionally substituted by COOH or in the 2- or 3-position by NH2, NHCOT, NHT, N(T)COT or N(T)2 ) or (c) a ring as in (a) or (b) having a fused phenyl or pyridine ring); imidazolidine-2,4-dion-5-yl (optionally substituted by 1 or 2 T, (optionally substituted by COOH)); 1-4C alkyl (substituted by T-Y1-A, HOOC-A-Y1-A, tetrazolyl-A-Y2, NR3R4, or A-NR3R4; isoxazolidinylcarbonyl (optionally substituted by T), pyrrolidino-carbonyl, 3,4-dehydropyrrolidino-carbonyl, pyrrol-1-ylcarbonyl, COOH or CONH2; CONHT, CON(T)2 or 4-7 membered cycloalkyleneiminocarbonyl (optionally substituted by 1 or 2 T (optionally substituted by COOH)); and one or more F); T or 3-5C cycloalkyl, (both substituted by NR5R6); or T (substituted by 2-4C alkanoyl or 5-7C cycloalkanoyl and by chloro-, bromo- or iodo-(1-3C) alkyl); R1 = OT, NH2, NHT or N(T)2 (T is optionally substituted by COOH); 4-7 membered cycloalkyleneimino or cycloalkenyleneimino (both optionally substituted by 1 or 2 T, (optionally substituted by OH, OT, COOH, O-A-COOH, N(T')-A-COOH, CO-N(T')-A-COOH or N(T')CON(T')-A-COOH)); 4-7 membered cycloalkyleneimino substituted by OH; 5-7C cycloalkyleneimino (optionally substituted by T), having a phenyl ring fused to two adjacent C; or morpholino, piperazino, N(T)-piperazino, pyrrolidino, 3,4-dehydropyrrolidino or pyrrol-1-yl; T' = H or T; R2 = phenyl, naphthyl, 5-membered heteroaryl (containing one N(T'), O and/or S; or 1 or 2 N) or 6-membered heteroaryl (containing 1-3 N), all optionally substituted by T (optionally substituted by COOH, -O-A-COOT' or -N(T')-A-COOH); X = O, N(T), N(OT), NNHT, NN(T)2, NNHCOT, NN(T)COT or 1-3C alkylidene (where T moieties are optionally substituted by COOH); R3 = H or T (optionally substituted by COOH); R4 = H, T-Y1-A-Y2, HOOC-A-Y1-A-Y2, T-Y2 or HOOC-A-Y2; or NR3R4 = 4-7 membered cycloalkyleneimino (optionally substituted by COOH, T or A-COOH); Y1 = direct bond, O, S, SO, SO2, N(T'), N(ACOOH), NHCO or NHCONH; Y2 = direct bond, CO, SO2, N(T'), N(ACOOH) or NHCO (where the CO of NHCO is bonded to NR3R4); R5 = H, T, 5-7C cycloalkyl, PHCO, PhSO2 or pyridinyl; R6 = T, A-COOH or CO-A-COOH; Rb = H or T; Rc = CN or amidino (optionally substituted by 1 or 2 T). An Independent claim is also included for the preparation of (I).
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