SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF VERAPAMIL ANALOGS WITH RESTRICTED MOLECULAR FLEXIBILITY

Several analogs of verapamil, which are characterized by a reduced mol ecular flexibility, have been synthesized. pharmacological activity ha s been evaluated on guinea-pig atria (negative chronotropic and inotro pic activities) and guinea-pig aorta strips (vasorelaxing activity), T heir ability to displace the calcium antagonist (-)-desmethoxyverapami l ((-)-[H-3]-D888) on kitten cardiac tissue has also been evaluated. T he pharmacological results are in accord with the previously reported models for negative inotropic and chronotropic activities of verapamil -like compounds, but fail to give information about the conformation(s ) that act on smooth muscle.