SELECTIVE CLASS-III ANTIARRHYTHMIC AGENTS .1. BIS(ARYLALKYL)AMINES

A series of bis(arylalkyl)amines is described and their effects on prolonging effective refractory period in isolated cardiac tissue listed. Most compounds prolonged the cardiac action potential without significantly altering the maximum rate of depolarization and may be defined as selective class III antiarrhythmic agents. It was found that a particularly advantageous structural feature was to have a methanesulfonamido moiety on both of the aryl rings. Thus, compound 16 [1-(4-methanesulfonamidophenoxy)-2-[N-(4-methanesulfonamidophenethyl)-N-methylamine]ethane] was selected for further investigations. The compound is highly potent and selective class III agent which acts by blockade of cardiac potassium channels. © 1990, American Chemical Society. All rights reserved.