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

Hyung Kook Lee; Yun Suk Lee; Eun Joo Roh; Hyewhon Rhim; Jae Yeol Lee; Kye Jung Shin

doi:10.1016/j.bmcl.2008.06.037

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. Epub 2008 Jun 14.

Authors

Hyung Kook Lee¹, Yun Suk Lee, Eun Joo Roh, Hyewhon Rhim, Jae Yeol Lee, Kye Jung Shin

Affiliation

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / drug effects
Calcium Channel Blockers / chemical synthesis*
Calcium Channel Blockers / chemistry
Calcium Channel Blockers / pharmacology*
Calcium Channels, T-Type / drug effects*
Combinatorial Chemistry Techniques
Disease Models, Animal
Drug Design
Mibefradil / pharmacology*
Mice
Molecular Structure
Phenylacetates / chemical synthesis*
Phenylacetates / chemistry
Phenylacetates / pharmacology*
Piperazines / chemical synthesis*
Piperazines / chemistry
Piperazines / pharmacology*

Substances

Calcium Channel Blockers
Calcium Channels, T-Type
Phenylacetates
Piperazines
Mibefradil