Ogawa K, Matsushita Y
Hanno Research Center, Taiho Pharmaceutical Co., Ltd., Saitama, Japan.
Chem Pharm Bull (Tokyo). 1992 Sep;40(9):2442-7. doi: 10.1248/cpb.40.2442.
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.
制备了一系列2,5-二取代的2,3-二氢-1,2,5-苯并噻二氮杂䓬-4(5H)-酮1,1-二氧化物衍生物，并评价了它们对哇巴因诱导的豚鼠心律失常的抗心律失常作用。在这个初步筛选系统中，大多数合成化合物显示出抗心律失常活性。在1,2,5-苯并噻二氮杂䓬-4(5H)-酮1,1-二氧化物的5-位上带有2-(N,N-二甲基氨基)乙基、2-(吡咯烷-1-基)乙基和2-氧代-2-(吗啉-4-基)乙基部分的一些化合物表现出强效抗心律失常活性。讨论了这些化合物的构效关系。
