Synthesis and Antiarrhythmic Activity of 2, 5-Disubstituted 2, 3-Dihydro-1, 2, 5-benzothiadiazepin-4(5H)-one 1, 1-Dioxides

Abstract

A series of 2, 5-disubstituted 2, 3-dihydro-1, 2, 5-benzothiadiazepin-4(5H)-one 1, 1-dioxide derivatives were prepared and evaluated for the antiarrhythmic effect on ouabain-induced arrhythmias in guinea pigs. Most of the synthesized compounds showed the antiarrhythmic activity in this primary screening system. Some of the compounds with 2-(N, N-dimethylamino)ethyl, 2-(pyrrolidin-1-yl)ethyl and 2-oxo-2-(morpholin-4-yl)ethyl moieties on the 5-position of 1, 2, 5-benzothiadiazepin-4(5H)-one 1, 1-dioxide exhibited a potent antiarrhythmic activity. THe structure-activity relationship of these compounds was discussed.