Synthesis and antiarrhythmic activity of 2,5-disubstituted 2,3-dihydro-1,2,5-benzothiadiazepin-4(5H)-one 1,1-dioxides.
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.
Ogawa
K
K
Hanno Research Center, Taiho Pharmaceutical Co., Ltd., Saitama, Japan.
Matsushita
Y
Y
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control; D001569:Benzodiazepines / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D006168:Guinea Pigs; D006571:Heterocyclic Compounds / Q000494:pharmacology; D008297:Male; D010042:Ouabain
D000889:Anti-Arrhythmia Agents; D006571:Heterocyclic Compounds; D001569:Benzodiazepines; D010042:Ouabain