title: Synthesis of the optically active trans-isomers of diltiazem and their cardiovascular effects and Ca-antagonistic activity.
abstract: Optically active trans-isomers of diltiazem were synthesized and their cardiovascular effects were evaluated in anesthetized dogs and in isolated guinea pig hearts. Both (+)-2 (2R,3S) and (-)-2 (2S,3R) were much less active than diltiazem (1, 2S,3S) with short duration of action. No substantial enantiomeric difference in activity was seen between them. Their Ca-antagonistic activities on Ca(2+)-induced contractions in K(+)-depolarized canine basilar arteries were also examined. Absolute stereochemistry of (+)-2 was determined to be 2R,3S by X-ray crystallographic analysis.
authors.affiliation: Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Date
authors.forename: K
authors.initials: K
authors.lastname: Okamura
authors.forename: K
authors.initials: K
authors.lastname: Aoe
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: H
authors.initials: H
authors.lastname: Kugita
authors.forename: S
authors.initials: S
authors.lastname: Murata
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Kikkawa
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D001775:Blood Circulation / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000031:analogs & derivatives / Q000494:pharmacology*; D004285:Dogs; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D013237:Stereoisomerism
chemical_list: D002121:Calcium Channel Blockers; D004110:Diltiazem