New amidino- or guanidino-substituted aminoacid derivatives, are nitrogen monoxide synthase inhibitors useful for treating cardiovascular, cerebrovascular or central or peripheral nervous system disorders

摘要

Amidino- or guanidino-substituted aminoacid derivatives (I) are new. Aminoacid derivatives of formula (I) and their salts are new. R1 = H or alkyl; one of A, A' = H and the other = dithiolanyl or an aryl or heterocyclic group of formula (a) - (f); R2-R4 = H, halo, OH, alkyl, alkoxy, CN, NO2 or NR8R9; R8, R9 = H, alkyl or COR10; or NR8R9 = Het; Het = optionally substituted 4-7 membered heterocycle containing 1-3 heteroatoms (i.e. the N already present and optionally 1 or 2 or O, N and S); R10 = H, alkyl, alkoxy or NR11R12; R11, R12 = H or alkyl; or NR11R12 = Het; R7 = H, alkyl or COR13; R13 = H, alkyl, alkoxy or NR14R15; R14, R15 = H or alkyl; or NR14R15 = Het; U = direct bond, O, S or NR16, or is absent; R16 = H or alkyl; R17-R19 = H, halo, OH, SR20, alkyl, alkoxy, CN, NO2 or NR21R22; R20 = H or alkyl; R21, R22 = H, alkyl or COR23 or NR21R22 = Het; R23 = H, alkyl, alkoxy or NR24R25; R24, R25 = H or alkyl; or NR24R25 = Het; R7 = H, alkyl or COR13; R13 = H, alkyl, alkoxy or NR14R15; Q = OR26, SR26 or phenyl substituted by one or more of halo, OH, alkyl, alkoxy, CN, NO2 or NR8R9; R26 = H or alkyl; R27 = H, alkyl or aralkyl; T = CH2 or CH2CH2; R28 = H, alkyl, aminoalkyl, mono- or dialkylaminoalkyl or aralkyl (optionally ring-substituted by one or more of OH, halo, alkyl, alkoxy, NO2 or NR29R30); R29, R30 = H, alkyl or COR31; or NR29R30 = Het; R31 = H, alkyl, alkoxy or NR32R33; R32, R33 = H or alkyl or NR32R33 = Het; R34, R35 = H, alkyl or aralkyl (optionally ring-substituted by one or more groups such as OH, halo, alkyl, alkoxy, NO2 or NR36R37); R36, R37 = H, alkyl or COR38 or NR36R37 = Het; R38 = H, alkyl, alkoxy or NR39R40; R39, R40 = H or alkyl or NR39R40 = Het; R41 = H, OH, alkyl or alkoxy; D = 1-6C alkyl; 5- or 6-membered carbocyclic or heterocyclic aryl, containing 0-4 of O, S and N and optionally substituted by one or more of 1-6C alkyl, 2-6C alkenyl and 1-6C alkoxy; NR42R43; or SR44; R42, R43 = H, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, CN, NO2 or NH2 or NR42R43 = 5- or 6-membered non-aromatic heterocycle formed from CH2, NH, O and S units; R44 = 1-6C alkyl (optionally monosubstituted by OH, halo, NH2, CN or aralkyl); X = (CH2)n, (CH2)nCO, O(CH2)p, S(CH2)p, CH=CH(CH2)p or CH=CH(CH2)nCO; n = 0-6; p = 1-6; W = O or NR45; Y = (CH2)t, (CH2)qS or (CH2)qNR46; R45, R46 = H or alkyl; t = 0-6; q = 2-6; V = (CH2)r, (CH2)rO(CH2)s, (CH2)rS(CH2)s, (CH2)rSO(CH2)s or (CH2)rSO2(CH2)s; r = 1-6; and s = 2-6.