title: Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2- (dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position.
abstract: In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hypertensive rats. The introduction of methyl, ethyl, isopropyl, benzyl, methoxy, ethoxy, phenoxy, and methylthio groups increased the antihypertensive activity and prolonged duration of action, whereas cyclohexyl, cyclopentoxy, tolyloxy, p-methoxyphenoxy and phenylthio derivatives were less active than diltiazem. Among them, the 8-benzyl and phenoxy derivatives showed the most potent and long-lasting antihypertensive action.
authors.affiliation: Research Institute, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yanagisawa
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Shimoji
authors.forename: T
authors.initials: T
authors.lastname: Kanazaki
authors.forename: K
authors.initials: K
authors.lastname: Mizutari
authors.forename: H
authors.initials: H
authors.lastname: Nishino
authors.forename: H
authors.initials: H
authors.lastname: Shiga
authors.forename: H
authors.initials: H
authors.lastname: Koike
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D004110:Diltiazem