| Literature DB >> 20673719 |
Kelly-Ann S Schlegel1, Zhi-Qiang Yang, Thomas S Reger, Youheng Shu, Rowena Cube, Kenneth E Rittle, Phung Bondiskey, Mark G Bock, George D Hartman, Cuyue Tang, Jeanine Ballard, Yuhsin Kuo, Thomayant Prueksaritanont, Cindy E Nuss, Scott M Doran, Steven V Fox, Susan L Garson, Richard L Kraus, Yuxing Li, Victor N Uebele, John J Renger, James C Barrow.
Abstract
The discovery and synthesis of 4,4-disubstituted quinazolinones as T-type calcium channel antagonists is reported. Based on lead compounds 2 and 3, a focused SAR campaign driven by the optimization of potency, metabolic stability, and pharmacokinetic profile identified 45 as a potent T-type Ca(2+) channel antagonist with minimized PXR activation. In vivo, 45 suppressed seizure frequency in a rat model of absence epilepsy and showed significant alterations of sleep architecture after oral dosing to rats as measured by EEG. Copyright 2010 Elsevier Ltd. All rights reserved.Entities:
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Year: 2010 PMID： 20673719 DOI： 10.1016/j.bmcl.2010.07.010
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823