Synthesis of halogen-substituted 1,5-benzothiazepine derivatives and their vasodilating and hypotensive activities.
In an attempt to improve the effectiveness and duration of the action of diltiazem (1), a 1,5-benzothiazepine calcium channel blocker, its derivatives (2) with halogen substituents on the fused benzene ring were synthesized. These compounds were evaluated for their effects on vertebral and coronary blood flows and antihypertensive activity. The structure-activity relationships are discussed. The 8-chloro derivative ((+)-2b), the most potent compound in this series, was selected for clinical evaluation as a cerebral vasodilating and antihypertensive agent.
Inoue
H
H
Organic Chemistry Research Laboratory, Tanabe Seiyaku Co. Ltd., Saitama, Japan.
Konda
M
M
Hashiyama
T
T
Otsuka
H
H
Takahashi
K
K
Gaino
M
M
Date
T
T
Aoe
K
K
Takeda
M
M
Murata
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003326:Coronary Circulation / Q000187:drug effects; D004110:Diltiazem / Q000031:analogs & derivatives*; D004285:Dogs; D006168:Guinea Pigs; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013841:Thiazepines / Q000138:chemical synthesis* / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D013841:Thiazepines; C056595:clentiazem; D004110:Diltiazem