SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF 2-(4-BENZHYDRYL-1-PIPERAZINYL)-1-PHENYLETHANOLS AS NEW CALCIUM BLOCKERS

A series of 2-(4-benzhydryl-1-piperazinyl)-1-phenylethanols (4) was sy nthesized and evaluated for calcium entry-blocking activity, assessed as inhibitory activity on calcium current in rat hippocampal pyramidal neurons by using a patch-clamp technique (10(-5) M), and cerebral vas odilating activity, assessed in terms of increase of vertebral blood f low after intravenous administration (1 mg/kg) in anesthetized dogs. A lkoxy substituents on the phenyl ring of the phenylethanol moiety conf erred potent calcium entry-blocking activity and potent cerebral vasod ilating activity. Among these compounds, 4i (NC-1100) was selected as the best analog. Some pharmacological properties of 4i are presented.