New use of fused di:hydro-pyridine(s) - in treatment of ulcerative colitis and Crohn's disease

摘要

Use of fused dihydropyridines of formula (I), their tautomers of formulae (Ia) and (Ib), and salts of these cpds. with acids, bases and complex formers, as agents for treatment of ulcerative colitis and Crohn's disease, is new. Where, Ph = phenyl; X = OR1, NHR2 or NR3R4; R1 = H or 1-10C alkyl (opt. substd. by Q, 3-10C cycloalkyl, 5-6C cycloalkenyl, 2-3C acyl or RSO2); Q = CN, OH, RO, RS, ROCO, NH2, RNH, (R)2N, PhO (opt. substd. by T), Ph (opt. substd. by T), or Het or indole (both opt. substd. by R); T = 1-3 gps. of halo, CF3, RO, OH, SH, RS, R, N3, NH2, RNH, (R)2N, 2-3C acylamino, 2-3C acyloxy or the vicinal gp. O(CH2)nO; R = 1-4C alkyl; n = 1 or 2; Het = a 5-6 membered, opt. unsatd. monocyclic heterocycle contg. up to 3 N, O or S heteroatoms; R2 = H, 3-6C alkenyl, 3-6C alkynyl, 3-6C cycloalkyl, 3-6C alkyl (fused to a benzo gp.), 3-6C cycloalkenyl, 1-10C alkyl (opt. substd. by Q, naphthoxy, 3-10C cycloalkyl (opt. bridged), 5-6C cycloalkenyl, 2-3C acyl or RSO2) or phenyl (opt. substd. by T); R3, R4 = as R2, esp. 1-6C alkyl (opt. substd. by phenyl (itself opt. substd. by T); or NR3R4 = 5-6 membered opt. satd. heteorcycle contg. up to two other N, O or S heteroatoms and opt. substd. by R, OH or (CH2)pR5; p = 0, 1, 2, 3, or 4; R5 = Ph or PhO (both opt. substd. by T); or naphthoxy; A = a gp. of formula (i)-(vii); R8 = H, RO or R; R6, R7 = H, OH, R, RO, NH2 or MeSO2NH; or R6+R7 = O(CH2)nO; R9 = H or R; and R10 = H or 2-phenyl-2-ethoxy carbonylacetyl. USE/ADVANTAGE - Most of the cpds. (I) are described in EP-37934 and EP-251194. Admin. is oral, topical or parenteral in doses of 0.05-500 mg per dose.