Synthesis and biological evaluation of 1,4-diazepane derivatives as T-type calcium channel blockers

Su Jin Gu; Jae Kyun Lee; Ae Nim Pae; Hye Jin Chung; Hyewon Rhim; So Yeob Han; Sun-Joon Min; Yong Seo Cho

doi:10.1016/j.bmcl.2010.03.084

Synthesis and biological evaluation of 1,4-diazepane derivatives as T-type calcium channel blockers

Bioorg Med Chem Lett. 2010 May 1;20(9):2705-8. doi: 10.1016/j.bmcl.2010.03.084. Epub 2010 Mar 28.

Authors

Su Jin Gu¹, Jae Kyun Lee, Ae Nim Pae, Hye Jin Chung, Hyewon Rhim, So Yeob Han, Sun-Joon Min, Yong Seo Cho

Affiliation

¹ Life/Health Division, Korea Institute of Science and Technology, PO Box 131, Cheongyang, Seoul 130-650, Republic of Korea.

PMID: 20382529
DOI: 10.1016/j.bmcl.2010.03.084

Abstract

We have synthesized and biologically evaluated 1,4-diazepane derivatives as T-type calcium channel blockers. In this study, we discovered compound 4s, a potential T-type calcium channel blocker with good selectivity over hERG and N-type calcium channels. In addition, it exhibited favorable pharmacokinetic characteristics for further investigation of T-type calcium channel related diseases.

Publication types

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

MeSH terms

Administration, Oral
Animals
Antihypertensive Agents / chemical synthesis
Antihypertensive Agents / chemistry*
Antihypertensive Agents / pharmacokinetics
Azepines / chemical synthesis*
Azepines / chemistry
Azepines / pharmacokinetics
Benzimidazoles / chemical synthesis*
Benzimidazoles / chemistry
Benzimidazoles / pharmacokinetics
Calcium Channel Blockers / chemical synthesis*
Calcium Channel Blockers / chemistry
Calcium Channel Blockers / pharmacokinetics
Calcium Channels, T-Type / chemistry*
Calcium Channels, T-Type / metabolism
Cell Line
Humans
Rats
Trans-Activators / metabolism
Transcriptional Regulator ERG

Substances

1,4-diazepane
Antihypertensive Agents
Azepines
Benzimidazoles
Calcium Channel Blockers
Calcium Channels, T-Type
ERG protein, human
Trans-Activators
Transcriptional Regulator ERG