Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers

Il Whea Ku; Sangwon Cho; Munikumar Reddy Doddareddy; Min Seok Jang; Gyochang Keum; Jung-Ha Lee; Bong Young Chung; Youseung Kim; Hyewhon Rhim; Soon Bang Kang

doi:10.1016/j.bmcl.2006.05.031

Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers

Bioorg Med Chem Lett. 2006 Oct 1;16(19):5244-8. doi: 10.1016/j.bmcl.2006.05.031. Epub 2006 Jul 28.

Authors

Il Whea Ku¹, Sangwon Cho, Munikumar Reddy Doddareddy, Min Seok Jang, Gyochang Keum, Jung-Ha Lee, Bong Young Chung, Youseung Kim, Hyewhon Rhim, Soon Bang Kang

Affiliation

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

PMID: 16876404
DOI: 10.1016/j.bmcl.2006.05.031

Abstract

Morpholin-2-one-5-carboxamide derivatives were prepared by using the one-pot Ugi multicomponent reaction and evaluated for blocking effects on T- and N-type Ca(2+) channels. Among them, compound 5i produced the highest potency (IC(50)=0.45+/-0.02 microM), while compounds 5d, 5f, 5k, 5n, 5o, and 6m produced relatively high potency as well as selectivity on T-type Ca(2+) channels. These novel scaffolds showed potent and selective T-type Ca(2+) channel blocking activities.

Publication types

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

MeSH terms

Animals
Calcium Channel Blockers / chemical synthesis*
Calcium Channel Blockers / pharmacology
Calcium Channels, N-Type / drug effects
Calcium Channels, T-Type / drug effects*
Cell Line
Humans
Inhibitory Concentration 50
Morpholines / chemical synthesis*
Morpholines / pharmacology*
Oocytes
Structure-Activity Relationship
Xenopus

Substances

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