New phenylalkyl derivs. - are angiotensin II antagonists used to treat hypertension, coronary insufficiency, angina, cns disorders etc.

摘要

Phenylalkyl derivs. of formula (I), and their isomer mixts. enantiomers, tautomers and salts, are new. In (I) n = 0 or 1; A = alkylene; B = O, C(O), CH(OH), S, SO, SO2, alkylene, 2-4C alkylidene, 1,1-cycloalkylene, or NH (opt. substd. by alkyl or 1-4C alkenoyl); Ra = Cl, Br, OH, RSO2O, PhSO2O, PhQSO2O or one of 10 N-contg. heterocyclic gps. defined in the specification. Rb = (a) CN, COOH, CF3CONH, CF3CONHCH2, CF3SO2NH, CF3SO2NHMe, RSO2NH, RSO2NHCH2, etc., or (b) 1H-tetrazolyl, 1H-tetrazolylalkyl, 1H-tetrazolylaminocarbonyl or triazole, all opt. substd. by R, CF3, PhQ or Ph3C; or (C) 1-6C alkyl sulphonylaminocarbonyl (opt. perfluoroinated in alkyl), 2-7C alkoxycarbonyl, aralkoxycarbonyl, pivaloyloxymethoxycarbonyl, phthalidylmethoxycarbonyl, ethoxycarbonyloxyethoxycarbonyl, methoxymethoxycarbonyl, cyclohexylcarbonylmethoxycarbonyl or (1,3-dioxa-2-oxo- 4-methyl-cyclopenten-5-yl)-methoxycarbonyl; Rc = H, R, ArQ, Ar, COOH or COCO; Rd = 1-10C alkyl; 2-10C alkenyl, 2-10C alkynyl, cycloalkyl, cycloalkylalkyl, phenyl (opt. mono- or disubstd. by F, Cl, Br, Me or MeO), biphenylyl, naphthyl or heteroaryl; Re, Rf = H, or Re, Rf may also be F, Cl, Br, R or RO; Q = 1-4C alkylene; R = 1-4C alkyl; cycloalkyl contains 3-7C; Aryl = phenyl (mono- or disubstd. by F, Cl, Br, OH, R, RO, PhQO, Ph, NO2, NH2, RNH, (R)2N, alkanoylamine, CN, COOH, ROCO, NH2CO, RNHCO, (R)2NCO, CF3, alkanoyl, NH2SO2, RNHSO2 or (R)2NSO2) or naphthyl; Heteroaryl = a 5-membered heteroaromatic ring (contg. (i) and NH, O or S gp.; (ii) NH and O, S or N, or (iii) NH and 2 or 3 N) or a 6-membered heteroaromatic ring (contg. 1-3N atoms), both opt. mono- or disubstd. by F, Cl, Br, R, RO, OH, Ph, NO2, NH2,RNH, (R)2N, alkanoylamine, CN, COOH, ROCO, NH2CO, RNHCO, (R)2NCO, CF3, alkanoyl, NH2SO2, RNHSO2 or (R)2NSO2; Ph = phenyl. USE - (I) Are angiotensin antagonists, esp. angiotensin II antagonists, useful in treatment of hypertension, coronary insufficiencies, ischaemic peripheral circulation disorders, angina, prevention of insufficiency following myocardial infarction, treatment of diabetic nephropathy, glaucoma, gastrointestinal disorders and bladder infections. (I) Are also useful in treatment of pulmonary disorders (e.g., lung oedema and bronchitis) prevention of arterial restenosis, and treatment of arteriosclerosis and diabetic angiopathy. They are also useful in treatment of depression, Alzheimer's disease, Parkinsons's disease, Bulimia and disorders of cognitive functions. Admin.is intravenous, in doses of 20-100 (esp. 30-70) mg/day, or oral, in doses of 50-200 (esp. 75-150)mg/day.