Use of fused di:hydro-pyridinyl phenyl acetic acid derivs. - as anti-proliferative agents in treatment of tumours

摘要

Use of fused dihydropyridine cpds. of formula (Ia), their tautomers of formulae (Ib) and (Ic), and salts of these cpds. with acids, bases and complex-formers, as agents with antiproliferative effect, is new. Ph = phenyl; X = OR1, NHR2 or NR3R4; R1 = H, or 1-10C alkyl (opt. substd. by one or more Q); Q = CN, OH, RO, RS, ROCO, NH2, NHR, N(R)2, PhO (opt. substd.), Ph (opt. substd.), Het (opt. substd.) indole (opt. substd.), 2-3C acyl, 3-10C cycloalkyl, 5-6C cycloalkenyl or RSO2; R = 1-4C alkyl; Het = an opt. unsatd. 5-6 membered heteroatom which contains up to 3 O, N or S heteratoms; R2 = H, 3-6C alkenyl, 3-6C alkynyl, 3-6C cycloalkyl, 3-6C alkyl (fused to a benzo gp.), 3-6C cycloalkyl, Ph, or 1-10C alkyl (opt. susbtd. by one or more Q or naphthoxy); R2, R3 = R2, esp. 1-6C alkyl (opt. subtd. by Ph (itself opt. substd.)); or NR3R4 = an opt. satd. 5-6 membered heterocycle (opt. contg. up to 2 other N, O or S heteroatoms) which is opt. substd. by R, OH or (CH2)pR5; p = 0-4; R5 = Ph or PhO (both opt. substd.) or naphthoxy; A = a gp. of formula (i)-(vii); R8 = H, R or RO; R6, R7 = H, OH, R, RO, NH2 or MeSO2NH; or R6+R7 = O(CH2)nO; R9 = H or R; R10 = H or 2-phenyl-2-ethoxycarbonylacetyl. USE/ADVANTAGE - Most (I) are known from EP--37934 or EP-251194. The cpds. can be used to treat tumours. Admin. is oral, parenteral or topical in doses of 0.05-500 mg.