1-Amino-omega-aryloxy substd. ethane and propane derivs. - with calcium antagonising activity e.g. for treating angina

摘要

Amines of formula (I) and their acid addn. salts are new (R is H, halo, methyl, hydroxy, 1-4C alkoxy or benzyloxy, n is 1 or 2, m is 2 or 3. A is COCH2CH2, CHOH.CH2CH2, CH2CH2CH2, CHOH.C(CH3)2CH2 or CO.C(CH3)2.CH2 with Ar attached to the left-hand side. R1, R2 is H, 1-4C alkyl, H, 5-6C cycloalkyl or H, 4-8C cycloalkylalkyl (except where A is CO.C(CH3)2 CH2 or CHOH.C(CH3)2.CH2); or is di(1-4C) alkyl, or together with N completes pyrrolidino, piperidino, hexamethyleneimino or morpholino. Ar is gp. (b) or (c), R3 is halo, nitro or methyl. R4 is 1-4C alkoxy, p is 0-2, q is 0-4, (p+q not over 4) but when A is COCH2CH2 or CHOH.CH2CH2, p and q cannot both be zero). Also new are the intermediates (III) and (V) (R'1, R'2 is di(1-4C) alkyl or completes a heterocyclic ring). (I) have calcium antagonising activity so are useful as antiangina, antiarrhythmic, antihypertensive and vasodilating agents. In mice, intravenous LD50 values were up to about 40 mg/kg and the usual oral dose is up to 500 mg taken 1-5 times a day.