4,5-DIPHENYLIMIDAZOLE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS ACYL COENZYME A: CHOLESTEROL-0-ACYL-TRANSFERASE (ACAT) INHIBITOR

摘要

The invention provides new diphenylimidazoles of formula (I) wherein: Ph is phenyl; and wherein A) when Z is 4,5-diphenylimidazol-2-ylthio, then p is zero and Y is a --(Ch2)m--X--(CH2)n-- group in which a) m and n being the same are 1 or 2 and X is (1), (2) or (3), wherein R is hydrogen or an optionally omega-hydroxy substituted C1-C10 alkyl chain, or b) m and n are 2 and X is (4), (5), (6) or (7), in which q is 1 or 2; or B) when Z is an aryloxy group unsubstituted or substituted by a substituent chosen from C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alcoxy, halogen, amino or an aryloxy group substituted by two substituents chosen from C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halogen, amino, nitro, C1-C6 alkoxy-carbonyl, di(C1-C6 alkyl) amino and --NHCONH-C1-C6 alkyl, or an aryloxy or arylthio group substituted by three sustituents chosen independently from hydroxy and C1-C6 alkyl, or a group chosen from 2-pyridyloxy, an optionally substituted imidazo[1,2-b]pyrazol-1-yl group, 2,3--dihydro-1H-imidazo[1,2--b]pyrazol-1-yl and (8) in which R1 is (9), (10) or (11), in which each of R2, R3 and R4 independently is hydrogen, C1-C4 alkyl or C1-C4 alkoxy; then p is zero or 1 and Y is a --(CH2)m--X--(CH2)n-- group wherein m and n are 1, X is a --(CH A)t-- group wherein A is hydrogen or hydroxy and t is zero or an integer of 1 to 10, or a group chosen from (12), (13), (14), (15) in which R is as defined above; or C) when Z is thiazolidin--2,4--dione--5--yl, then p is zero and Y is a bond or a --(CH2)m--X--(CH2)n-- group in which m and n are 1, X is a --(CH2)t-- group in which t is as defined above, and the pharmaceutically acceptable forming salts thereof, which have an ACAT inhibiting activity and are thus useful in the treatment of dyslipidemia, atherosclerosis and coronary diseases.