Synthesis and biological evaluation of novel T-type Ca2+ channel blockers

Hee Kyung Jung; Munikumar Reddy Doddareddy; Joo Hwan Cha; Hyewhon Rhim; Yong Seo Cho; Hun Yeong Koh; Bong Young Jung; Ae Nim Pae

doi:10.1016/j.bmc.2004.06.011

Synthesis and biological evaluation of novel T-type Ca2+ channel blockers

Bioorg Med Chem. 2004 Aug 1;12(15):3965-70. doi: 10.1016/j.bmc.2004.06.011.

Authors

Hee Kyung Jung¹, Munikumar Reddy Doddareddy, Joo Hwan Cha, Hyewhon Rhim, Yong Seo Cho, Hun Yeong Koh, Bong Young Jung, Ae Nim Pae

Affiliation

¹ Lifescience Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.

PMID: 15246072
DOI: 10.1016/j.bmc.2004.06.011

Abstract

A small molecule library of piperazinylalkylisoxazole derivatives containing about 600 compounds was designed, synthesized and evaluated for blocking effects on T-type Ca(2+) channel. Several ligands were identified to possess high inhibitory activity against the T-type Ca(2+) channel. The compound 21 with trifluoromethyl substituents at C(3)-position of phenyl group (R(1)) and C(2)-position of phenyl group (R(2)) showed the highest inhibitory activity with IC(50) value of 1.02 microM, which is comparable to that of mibefradil.

Publication types

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

MeSH terms

Calcium / chemistry
Calcium / metabolism
Calcium Channel Blockers / chemical synthesis*
Calcium Channel Blockers / chemistry
Calcium Channel Blockers / pharmacology*
Calcium Channels, T-Type / drug effects*
Calcium Channels, T-Type / metabolism
Cell Line
Drug Design
Humans
Isoxazoles / chemical synthesis*
Isoxazoles / chemistry
Isoxazoles / pharmacology*
Ligands
Molecular Structure
Piperazines / chemical synthesis*
Piperazines / chemistry
Piperazines / pharmacology*
Structure-Activity Relationship

Substances

Calcium Channel Blockers
Calcium Channels, T-Type
Isoxazoles
Ligands
Piperazines
Calcium