MONO(AMINOMETHYL)PHENYLACETIC AND BIS(AMINOMETHYL)PHENYLACETIC ACID-ESTERS AS SHORT-ACTING ANTIARRHYTHMIC AGENTS .2.

被引：6

作者：

CHORVAT, RJ

BLACK, LA

RANADE, VV

BARCELONYANG, C

STOUT, DM

BROWN, BS

STAMPFLI, HF

QUON, CY

机构：

[1] DUPONT MERCK PHARMACEUT CO,DEPT PHARMACOL,WILMINGTON,DE 19880

[2] STINE HASKELL RES CTR,DEPT DRUG METAB & PHARMACOKINET,NEWARK,DE 19880

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 17期

关键词：

D O I：

10.1021/jm00069a007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis, antiarrhythmic activity, and blood hydrolysis properties of a series of mono- and bis(aminomethyl)phenylacetic acid esters related to a previously reported class Ic antiarrhythmic agent (ACC-9358) are described. Of the various oxa-, aza-, thia-, and carbacyclic esters initially prepared in the bis(pyrrolidinomethyl)-4-hydroxyphenylacetic acid series, the 1,4-benzodioxanyl-2-methyl (3q) and the thienyl-2-methyl (31) esters were evaluated in vivo for antiarrhythmic efficacy. In addition, a number of monoappended phenylacetic esters of 3q with or without the 4-hydroxy group were also prepared for evaluation of antiarrhythmic, lipophilic, and metabolic properties. Of these compounds, 3q possessed the most desirable pharmacological and pharmacokinetic profile.

引用

页码：2494 / 2498

页数：5

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