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

  • Bioorg Med Chem Lett. 2008 Aug 1;18(15):4424-7. doi: 10.1016/j.bmcl.2008.06.037.
Hyung Kook Lee  1 ,  Yun Suk Lee ,  Eun Joo Roh ,  Hyewhon Rhim ,  Jae Yeol Lee ,  Kye Jung Shin
Affiliations
  • 1. Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongyang, Seoul 130-650, Republic of Korea.
PMID: 18625556 DOI: 10.1016/j.bmcl.2008.06.037
Abstract

We have synthesized and evaluated alpha,alpha'-disubstituted phenylacetate derivatives that were designed as T-type calcium channel blockers. Among them, compound 10e (IC(50)=8.17+/-0.48nM) showed the most potent T-type calcium current blocking activity and higher potency than Mibefradil (IC(50)=1.34+/-0.49microM). The PK profile and subtype selectivity over L-type calcium channel were satisfied for further animal assay using disease model.