ENDOTHELIN RECEPTOR ANTAGONISTS

摘要

Indane and indene derivs. of formula (I) and their salts are new. In (I), R1 = X(CH2)nAr, X(CH2)nR8 or a gp. (a); R2 = H, Ar or (a); P1 = X(CH2)nR8; P2 = X(CH2)nR8 or XR9Y; R3, R5 = R11, H, OH, 1-8 alkoxy, S(O)qR11, N(R6)2, Br, F, I, Cl, CF3, NHCOR6, X(R9)Y or X(CH2nR8; (opt. substd). R4 = H, R11, OH, S(O)qR11, N(R6)2, XR11, Br, F, Il Cl, NHCOR6 or 1-5C alkoxy (opt. substd.) R6 = H or 1-4C alkyl; R7 = H, 1-6C alkyl or (CH2)nAr; R8 = H, R11, CO2H, PO3H2, P(O)(OH)R7 or tetrazole; R9 = HOC alkyl, 2-10C alkenyl or phenyl all opt. substd. by OH, N(R6)2, CO2H, halo and/or X - 1-5C alkyl; R10 = R3 or R4; R11 = 1-8C alkyl, 2-8C alkenyl or 2-8C alkynyl all opt. substd. by OH, CH2OH, N(R6)2 and/or halo; X = (CH2)n, O, NR6 or S(O)q; Y = Me or CH2X(CH2)nAr; Ar = phenyl (opt. substd) a gp. of formula (b); naphthyl, indolyl pyridinyl orthienyl, oxazolidinyl, oxadolyl, thiazolyl, isothiazolyl, pyrazolyl triazolyl, tetrazolyle, imidazolyl, imidazolidinyl, thiazolidinyl, isoxazolyl, oxadiazolyl, thiadiazolyl, morpholinyl, piperidinyl, piperavinyl, pyrrolyl or pyrimidyl (all opt. substd). A = C(=O) or (C(R6)2)m; B = CH2 or O; Z1, Z2 = H, 1-8C alkyl, 2-8C cycloalkenyl, 2-8C alkynyl, OH, 1-8C alkoxy, S(O)q 1-8C alkyl, N(R6)2, Br, F, I, Cl, NHCOR6, -X(CH2)nR8, phenyl, benzyl or 2-8C alkynyl, (opt. substd. by COOH, OH, CO(CH2)nMe, CO(CH2)nCH2N(R6)2 or halo; or Z1 + Z2 = O-AO (on contiguous C atoms); R3 = Z1 or XR9Y; q = 0, 1 or 2; n = 0-6; and m = 1-3; wth provisos.