Synthesis and antiarrhythmic activity of alpha, alpha-bis[(dialkylamino)alkyl]phenylacetamides.

The synthesis and biological evaluation of a series of alpha, alpha-bis[(dialkylamino)alkyl]phenylacetamides, 2, are presented. These compounds are structurally related to the antiarrhythmic agent disopyramide (1) and in many cases were found to possess greater antiarrhythmic activity in coronary ligated dogs. Within this series of compounds, a separation of the antiarrhythmic properties from the unwanted cardiac depressant side effects observed with the parent compound, 7, was also often attained. A discussion of the structure-activity relationships within the series is presented; this work has culminated in the identidiction of compound 35 (disobutamide) as a candidate for clinical evaluation as an antiarrhythmic agent in man.