Novel T-type calcium channel blockers: Dioxoquinazoline carboxamide derivatives

Abstract

T-type calcium channel is one of therapeutic targets for the treatment of cardiovascular diseases and neuropathic pains. Since the withdrawal of mibefradil, a T-type calcium channel blocker, there have been a lot of efforts to develop T-type calcium channel blockers. A small molecule library of dioxoquinazoline carboxamide derivatives containing 155 compounds was designed, synthesized, and biologically evaluated for T-type calcium channel blocking activity. Among those compounds synthesized, the compound In shows the most potent T-type calcium current blocking activity with an IC50 value of 1.52 mu M, which is comparable to that of mibefradil. (c) 2006 Elsevier Ltd. All rights reserved.