Inoue H, Konda M, Hashiyama T, Otsuka H, Takahashi K, Gaino M, Date T, Aoe K, Takeda M, Murata S
Organic Chemistry Research Laboratory, Tanabe Seiyaku Co. Ltd., Saitama, Japan.
J Med Chem. 1991 Feb;34(2):675-87. doi: 10.1021/jm00106a032.
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.
