Discovery of 4,4-Disubstituted Ouinazolin-2-ones as T-Type Calcium Channel Antagonists
作者
BARROW JAMES C; RITTLE KENNETH E; REGER THOMAS S; YANG ZHIQIANG; 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; GRAUFELDS VALERIE KUZMICK; UEBELE VICTOR N; RENGER JOHN J
[摘要]：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 and selective antagonists that displayed in vivo central nervous system efficacy in epilepsy and tremor models, as well as significant effects on rat active wake as measured by electrocorticogram.
