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

The synthesis, antiarrhythmic activity, and blood hydrolysis propertie s of a series of mono- and bis(aminomethyl)phenylacetic acid esters re lated to a previously reported class Ic antiarrhythmic agent (ACC-9358 ) are described. Of the various oxa-, aza-, thia-, and carbacyclic est ers initially prepared in the bis(pyrrolidinomethyl)-4-hydroxyphenylac etic acid series, the 1,4-benzodioxanyl-2-methyl (3q) and the thienyl- 2-methyl (31) esters were evaluated in vivo for antiarrhythmic efficac y. In addition, a number of monoappended phenylacetic esters of 3q wit h or without the 4-hydroxy group were also prepared for evaluation of antiarrhythmic, lipophilic, and metabolic properties. Of these compoun ds, 3q possessed the most desirable pharmacological and pharmacokineti c profile.