910484-13-8Relevant academic research and scientific papers
Discovery and expanded SAR of 4,4-disubstituted quinazolin-2-ones as potent T-type calcium channel antagonists
Schlegel, Kelly-Ann S.,Yang, Zhi-Qiang,Reger, Thomas S.,Shu, Youheng,Cube, Rowena,Rittle, Kenneth E.,Bondiskey, Phung,Bock, Mark G.,Hartman, George D.,Tang, Cuyue,Ballard, Jeanine,Kuo, Yuhsin,Prueksaritanont, Thomayant,Nuss, Cindy E.,Doran, Scott M.,Fox, Steven V.,Garson, Susan L.,Kraus, Richard L.,Li, Yuxing,Uebele, Victor N.,Renger, John J.,Barrow, James C.
scheme or table, p. 5147 - 5152 (2010/12/18)
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 Ca2+ 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.
Discovery of 4,4-disubstituted quinazolin-2-ones as T-type calcium channel antagonists
Barrow, James C.,Rittle, Kenneth E.,Reger, Thomas S.,Yang, Zhi-Qiang,Bondiskey, Phung,McGaughey, Georgia B.,Bock, Mark G.,Hartman, George D.,Tang, Cuyue,Ballard, Jeanine,Kuo, Yuhsin,Prueksaritanont, Thomayant,Nuss, Cindy E.,Doran, Scott M.,Fox, Steven V.,Garson, Susan L.,Kraus, Richard L.,Li, Yuxing,Marino, Michael J.,Kuzmick Graufelds, Valerie,Uebele, Victor N.,Renger, John J.
scheme or table, p. 75 - 79 (2010/11/17)
A novel series of quinazolinone T-type calcium channel antagonists have been prepared and evaluated using in vitro and in vivo assays. Optimization of the screening hit 3 by modifications of the 3- and 4-positions of the quinazolinone ring afforded potent
QUINAZOLINONE T-TYPE CALCIUM CHANNEL ANTAGONISTS
-
Page/Page column 32; 33, (2009/03/07)
The present invention is directed to quinazolinone compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is al
QUINAZOLINONE T-TYPE CALCIUM CHANNEL ANTAGONISTS
-
Page/Page column 24-26, (2010/11/23)
The present invention is directed to quinazolinone compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.
