Synthesis of the optically active trans-isomers of diltiazem and their cardiovascular effects and Ca-antagonistic activity.
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.
Tanaka
T
T
Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Inoue
H
H
Date
T
T
Okamura
K
K
Aoe
K
K
Takeda
M
M
Kugita
H
H
Murata
S
S
Yamaguchi
T
T
Kikkawa
K
K
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
D002121:Calcium Channel Blockers; D004110:Diltiazem