A New Class of Calcium Antagonists. Synthesis and Biological Activity of 11--6,6a,7,8,9,10,10a,11-octahydrodibenzothiepin Derivatives

Article abstract of DOI:10.1021/jm00106a019

A series of 11-<(ω-aminoalkanoyl)amino>-6,6a,7,8,9,10,10a,11-octahydrodibenzothiepin derivatives were prepared and found to be structurally new class of calcium antagonists.The structure-activivty relationship studies indicated that the optimum was (6aR^*,10aR^*,11R^*)-11-<<4-<-<4-(4-fluorophenyl)-1-piperazinyl>butyryl>amino>-6,6a,7,8,9,10,10a,11-octahydrodibenzothiepin (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-elevation testings in rats.These potencies of 31 were essentially equal to those of diltiazem.