A NEW CLASS OF CALCIUM-ANTAGONISTS - SYNTHESIS AND BIOLOGICAL-ACTIVITY OF 11-[(OMEGA-AMINOALKANOYL)AMINO]-6,6A,7,8,9,10,10A,11-OCTAHYDRODIBENZO[B,E]THIEPIN DERIVATIVES

被引：13

作者：

KUROKAWA, M ^{[1
]}

SATO, F ^{[1
]}

HATANO, N ^{[1
]}

HONDA, Y ^{[1
]}

UNO, H ^{[1
]}

机构：

[1] DAINIPPON PHARMACEUT CO LTD, RES LABS, ENOKI 33-94, SUITA, OSAKA 564, JAPAN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 02期

关键词：

D O I：

10.1021/jm00106a019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 11-[(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11?? -octahydrodibenzo[b,e]thiepin derivatives were prepared and found to be a structurally new class of calcium antagonists. The structure-activity relationship studies indicated that the optimum was (6aR*, 10aR*, 11R*)-11-[[4-[4-(4-fluorophenyl)-1-piperazinyl]butyryl]amino]-6,6a7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin (31, pA2 8.16), which was superior to diltiazem (pA2 7.42) in calcium antagonistic activity. Compound 31 showed antihypertensive activity in anesthetized rats, without a significant effect on the heart rate. It had also antianginal effects in vasopressin-induced ST-depression and methacholine-induced ST-elevation testings in rats. These potencies of 31 were essentially equal to those of diltiazem.

引用

页码：593 / 599

页数：7

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