Synthesis and evaluation of α, α′-disubstituted phenylacetate derivatives for T-type calcium channel blockers

HK Lee, YS Lee, EJ Roh, H Rhim, JY Lee…

Index: Lee, Hyung Kook; Lee, Yun Suk; Roh, Eun Joo; Rhim, Hyewhon; Lee, Jae Yeol; Shin, Kye Jung Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 15 p. 4424 - 4427

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Citation Number: 16

Abstract

We have synthesized and evaluated α, α′-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 μM). The PK profile and subtype selectivity over L- type calcium channel were satisfied for further animal assay using disease model.