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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.

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