Novel T-type calcium channel blockers: dioxoquinazoline carboxamide derivatives.

Abstract

T-type calcium channel is one of therapeutic targets for the treatment of cardiovascular diseases and neuropathic pains. Since the withdrawal of mibefradil, a T-type calcium channel blocker, there have been a lot of efforts to develop T-type calcium channel blockers. A small molecule library of dioxoquinazoline carboxamide derivatives containing 155 compounds was designed, synthesized, and biologically evaluated for T-type calcium channel blocking activity. Among those compounds synthesized, the compound 1n shows the most potent T-type calcium current blocking activity with an IC(50) value of 1.52 microM, which is comparable to that of mibefradil.

• Authors: Mi Na Jo, Hee Jeong Seo, Yoonji Kim, Seon Hee Seo, Hyewhon Rhim, Yong Seo Cho, Joo Hwan Cha, Hun Yeong Koh, Hyunah Choo, Ae Nim Pae
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 1 Pg. 365-73 (Jan 01 2007) ISSN: 0968-0896 [Print] England
• PMID: 17035033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Calcium Channel Blockers
• Calcium Channels, T-Type
• Quinazolines

Topics

• Amides (chemical synthesis, chemistry, pharmacology)
• Calcium Channel Blockers (chemical synthesis, chemistry, pharmacology)
• Calcium Channels, T-Type (drug effects)
• Cell Line
• Drug Design
• Drug Evaluation, Preclinical
• Humans
• Molecular Structure
• Quinazolines (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism
• Structure-Activity Relationship