Synthesis and Biological Evaluation of Novel Pyrazole Derivatives as T-type Calcium Channel Blockers

Abstract

T-type calcium channels have been studied extensively as targets of neuropathic pain, hypertension and epilepsy pectoris. As an effort to develop potent T-type calcium channel blockers, we previously studied piperazinylalkylpyrazole structure. But we needed compounds of improved diological activity. Experting improved activity, therefore, we changed the former structure slightly to piperazinylalkycarboxamidopyrazole structure, and constructed a pyrazole library through solution phase combinatorial synthesis. Their α1G calcium channel and hERE channel blocking activity were evaluated. Several compounds showed high blocking effects on T-type (α1G) calcium channels. The structure-activity relationships will be presented.