Synthesis and evaluation of alpha,alpha'-disubstituted phenylacetate derivatives for T-type calcium channel blockers

Abstract

We have synthesized and evaluated alpha,alpha'-disubstituted phenylacetate derivatives that were designed as T-type calcium channel blockers. Among them, compound 10e (IC50 = 8.17 +/- 0.48 nM) showed the most potent T-type calcium current blocking activity and higher potency than Mibefradil (IC50 = 1.34 +/- 0.49 mu M). The PK profile and subtype selectivity over L-type calcium channel were satisfied for further animal assay using disease model. (c) 2008 Elsevier Ltd. All rights reserved.