Novel T-type calcium channel blockers: Dioxoquinazoline carboxamide derivatives

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 1n shows the most potent T-type calcium current blocking activity with an IC50 value of 1.52 μM, which is comparable to that of mibefradil.

A small molecule library of dioxoquinazoline carboxamide derivatives 1 was synthesized and biologically evaluated for T-type calcium channel blocking activity.Figure optionsDownload as PowerPoint slide