| 摘要 |
2-(2-(4-(Amidino or aminomethyl)-phenyl)-ethyl)-benzimidazole-5-carboxylic acid cyclic amide derivatives (I) are new. Also new are 4-cyano-phenyl analog intermediates (III). 2-(2-(4-(Amidino or aminomethyl)-phenyl)-ethyl)-benzimidazole-5-carboxylic acid cyclic amide derivatives of formula (I) (including tautomers, racemates, enantiomers, diastereomers and their mixtures) and their acid addition salts are new. R<1> = 1-10C alkyl or 3-6C cycloalkyl (both optionally substituted (os) by 1-3 of OT, OPh, hydroxyphenoxy, 1-4C alkoxyphenoxy, 3-6C cycloalkyl, NH2, NHT, NT2, NHCOT, CONH2, CONHT or NHCOCH2Ph), phenyl-(1-4C) alkyl (os in the ring by 1-3 of T, CF3, F, Cl, Br, COOH or COOT), Het or Het-(1-4C) alkyl; T = 1-4C alkyl; Het = 5- or 6-membered, saturated or unsaturated heterocyclyl, which (i) contains 1-3 heteroatoms selected from O, N and S, (ii) is os by 1-3 of T, phenyl (os by T) or benzyl (os by T) and (iii) is optionally fused via two adjacent C-atoms to a benzene ring; R<2> = C(=NH)NH2 or CH2NH2, or a prodrug residue of formula C(=NR<6>)NH2; A = 4-7 membered saturated heterocyclyl, containing 1 or 2 N and optionally 1 or 2 of O and S as heteroatom(s); R<3> = NR<4>R<5>, CH2CH2-Ph or CH=CH-Ph, or phenyl substituted by one or more of halo, CF3 and NO2; R<4> = H or B'-(CH2)r-X; R<5> = D-(CH2)t; B', D = 1-6C alkyl, 1-6C haloalkyl, 2-6C alkenyl, 2-6C alkynyl, (1-6C) alkoxy-(1-6C) alkyl, 3-8C cycloalkyl, or (1-4C) alkylenedioxyphenyl, or phenyl, naphthyl or Het' (all os by one or more of halo, NO2, CN, T', OT', ST', SO2T, OPO2-T, 1-5C alkanoyl, COOT, T-CN, T-OH, T-OT, COOH, NH2, NHT, NT2, SO2NH2, Ph or OH), or NR<4>R<5> = 4-10 membered saturated heterocyclyl or spiro-heterocyclyl, optionally containing a further O, S or N heteroatom, optionally having 1 or 2 CH2 groups replaced by CO or CS and os by one or more of T, 3-8C cycloalkyl, CH2Ph (os by T), pyridyl or Ph (os by T, OT or OH); X = CO, NHCO, SO2, NHSO2 or a direct bond; r, t = 0 or 1; Het' = 5- or 6-membered heterocyclyl containing 1-3 heteroatoms selected from O, N and S; T' = T or 1-4C haloalkyl; R<6> = OH, OU, OCOOU, CO(O)sU, CO(O)s-(1-4C) haloalkyl, CO(O)s-T-OCOT, CO(O)sPh', CO(O)s-pyridyl, CO(O)s-(2-4C) alkenyl-Ph' or CO(O)s-T-Ph'; U = 1-8C alkyl; Ph = phenyl (os by T', NHT, NT2, OT', COT or OCOT), and s = 0 or 1. Independent claims are included for: (1) preparation of (I); and (2) new nitrile intermediates of formula (III).
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