title: 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.
abstract: 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]-6,6a,7,8,9,10,10a,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.
authors.affiliation: Research Laboratory, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.forename: F
authors.initials: F
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Hatano
authors.forename: Y
authors.initials: Y
authors.lastname: Honda
authors.forename: H
authors.initials: H
authors.lastname: Uno
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003988:Dibenzothiepins / Q000138:chemical synthesis* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D002121:Calcium Channel Blockers; D003988:Dibenzothiepins