New benzazepine derivatives useful for treating or preventing dyslipidemia, arteriosclerosis, restenosis and ischemia

摘要

Benzazepine derivatives (I) are new. Benzazepine derivatives of formula (I) and their salts and solvates are new. A : 6-10C aryl or 5- to 10-membered heteroaryl, each optionally substituted with 1-3 of halo, CN, NO 2, CF 3, OCF 3, 1-6C alkyl and 1-6C alkoxy; or 2,3-ethylenedioxyphenyl or 2,3-methylenedioxyphenyl; n : 1-3; R 1, R 2H, halo, CN, NO 2, CF 3, OCF 3, 1-6C alkyl or 1-6C alkoxy; R 31-8C alkyl, 2-8C alkenyl or 2-8C alkynyl, each optionally substituted with phenyl, 3-8C cycloalkyl, OH or NH 2; R 4OR 7 or NR 8R 9; R 7H or 1-6C alkyl; R 8, R 9H, 1-6C alkyl or 3-8C cycloalkyl, each optionally substituted with COOH, 1-6C alkoxycarbonyl, CONH 2 or mono- or di(1-6C alkyl)carbamoyl, or NR 8R 9 is a 4- to 8-membered heterocycle optionally containing another heteroatom (NR 10, O, S, SO or SO 2) and optionally substituted with OH, oxo, NH 2, 1-6C alkyl, COOH, 1-6C alkoxycarbonyl, CONH 2 or mono- or di(1-6C alkyl)carbamoyl, where alkyl is optionally substituted with OH, NH 2, COOH, 1-6C alkoxycarbonyl, CONH 2 or mono- or di(1-6C alkyl)carbamoyl; R 10H, 1-4C alkyl, 1-4C acyl or 1-4C alkoxycarbonyl. Independent claims are also included for: (1) a process for preparing compounds (I); (2) medicament comprising a compound (I) and optionally a cholesterol-lowering statin, a cholesterol absorption inhibitor, a HDL-increasing, triglyceride-lowering and/or apolipoprotein B-lowering substance, an oxidation inhibitor or an antiinflammatory agent. [Image] ACTIVITY : Antilipemic; Antiarteriosclerotic; Vasotropic. MECHANISM OF ACTION : Squalene synthase inhibitor; Squalene synthesis inhibitor; Cholesterol synthesis inhibitor. Compounds cited in examples had IC50 values below 20 microM for inhibiting microsomal squalene synthase activity.