title: Discovery of 4,4-Disubstituted Quinazolin-2-ones as T-Type Calcium Channel Antagonists.
abstract: 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.
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: James C
authors.initials: JC
authors.lastname: Barrow
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Rittle
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Reger
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yang
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Phung
authors.initials: P
authors.lastname: Bondiskey
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Georgia B
authors.initials: GB
authors.lastname: McGaughey
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Bock
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.affiliation: Drug Metabolism and Pharmacokinetics.
authors.forename: Cuyue
authors.initials: C
authors.lastname: Tang
authors.affiliation: Drug Metabolism and Pharmacokinetics.
authors.forename: Jeanine
authors.initials: J
authors.lastname: Ballard
authors.affiliation: Drug Metabolism and Pharmacokinetics.
authors.forename: Yuhsin
authors.initials: Y
authors.lastname: Kuo
authors.affiliation: Drug Metabolism and Pharmacokinetics.
authors.forename: Thomayant
authors.initials: T
authors.lastname: Prueksaritanont
authors.affiliation: Depression and Circadian Disorders.
authors.forename: Cindy E
authors.initials: CE
authors.lastname: Nuss
authors.affiliation: Depression and Circadian Disorders.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Doran
authors.affiliation: Depression and Circadian Disorders.
authors.forename: Steven V
authors.initials: SV
authors.lastname: Fox
authors.affiliation: Depression and Circadian Disorders.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Garson
authors.affiliation: Depression and Circadian Disorders.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kraus
authors.affiliation: Depression and Circadian Disorders.
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Parkinson's Disease.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Marino
authors.affiliation: Parkinson's Disease.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kuzmick Graufelds
authors.affiliation: Depression and Circadian Disorders.
authors.forename: Victor N
authors.initials: VN
authors.lastname: Uebele
authors.affiliation: Depression and Circadian Disorders.
authors.forename: John J
authors.initials: JJ
authors.lastname: Renger
keywords: Quinazolin-2-ones; T-type calcium channel; calcium channel antagonists; electrocorticogram; epilepsy; tremor