SUBSTITUTED 3-AMINO-1,1-DIARYL-2-PROPANOLS AS POTENTIAL ANTI-DEPRESSANT AGENTS

被引：12

作者：

CLARK, JA ^{[1
]}

CLARK, MSG ^{[1
]}

GARDNER, DV ^{[1
]}

GASTER, LM ^{[1
]}

HADLEY, MS ^{[1
]}

MILLER, D ^{[1
]}

SHAH, A ^{[1
]}

机构：

[1] BEECHAM PHARMACEUT,DIV RES,MED RES CTR,HARLOW CM19 5AD,ESSEX,ENGLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1979年 / 22卷 / 11期

关键词：

D O I：

10.1021/jm00197a018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Following the discovery that 3-(dimethylamino)-l, l-diphenyl-2-propanol hydrobromide (1) possesses potent reserpine-prevention activity in mice, a series of analogues of 1 was synthesized and evaluated as potential antidepressant agents. Several routes to analogues of 1 were evaluated, the most generally applicable of which was the regiospecific ring opening of a suitably functionalized l, l-diaryl-2, 3-epoxypropane (obtained in three stages from the corresponding benzophenone) with the appropriate amine. The more interesting compounds of the series were evaluated for their propensity to cause undesirable peripheral anticholinergic effects, all compounds tested being markedly less active than imipramine on this parameter. On the basis of its good activity in biochemical and pharmacological animal models of depression, together with its relative lack of anticholinergic side effects, l-(3-chlorophenyl)-3-(dimethylamino)-l-phenyl-2-propanol hydrochloride (20, BRL 14342) was chosen for further evaluation. © 1979, American Chemical Society. All rights reserved.

引用

页码：1373 / 1379

页数：7