Synthesis and biological activity of 3,4-dihydroquinazolines for selective T-type Ca2+ channel blockers

Hyewhon Rhim; Yong Sup Lee; Seong Jun Park; Bong Young Chung; Jae Yeol Lee

doi:10.1016/j.bmcl.2004.10.078

Synthesis and biological activity of 3,4-dihydroquinazolines for selective T-type Ca2+ channel blockers

Bioorg Med Chem Lett. 2005 Jan 17;15(2):283-6. doi: 10.1016/j.bmcl.2004.10.078.

Authors

Hyewhon Rhim¹, Yong Sup Lee, Seong Jun Park, Bong Young Chung, Jae Yeol Lee

Affiliation

¹ Life Sciences Division, Korea Institute of Science & Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.

PMID: 15603940
DOI: 10.1016/j.bmcl.2004.10.078

Abstract

We have synthesized 3,4-dihydroquinazoline derivatives for the potent and selective T-type Ca(2+) channel blockers and evaluated for their inhibitory activities against two subtypes T-type Ca(2+) channels and N-type Ca(2+) channels. Among them, 5b (KYS05044, IC(50)=0.56+/-0.10 microM) was identified as potent T-type Ca(2+) channel blocker with in vitro selectivity profile at meaningful level (T/N-type, SI=>100).

Publication types

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

MeSH terms

Calcium Channel Blockers / chemical synthesis*
Calcium Channel Blockers / pharmacology
Calcium Channels, N-Type / drug effects*
Calcium Channels, N-Type / metabolism
Calcium Channels, T-Type / drug effects*
Calcium Channels, T-Type / metabolism
Cell Line
Inhibitory Concentration 50
Molecular Structure
Oocytes / drug effects*
Quinazolines / chemical synthesis
Quinazolines / pharmacology

Substances

Calcium Channel Blockers
Calcium Channels, N-Type
Calcium Channels, T-Type
Quinazolines