title: Discovery of Oxazolobenzimidazoles as Positive Allosteric Modulators for the mGluR2 Receptor.
abstract: Novel oxazolobenzimidazoles are described as potent and selective positive allosteric modulators of the metabotropic glutamate receptor 2. The discovery of this class and optimization of its physical and pharmacokinetic properties led to the identification of potent and orally bioavailable compounds (20 and 21) as advanced leads. Compound 20 (TBPCOB) was shown to have robust activity in a PCP-induced hyperlocomotion model in rat, an assay responsive to clinical antipsychotic treatments for schizophrenia.
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Garbaccio
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Brnardic
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Fraley
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.affiliation: Psychiatry Research.
authors.forename: Pete H
authors.initials: PH
authors.lastname: Hutson
authors.affiliation: In Vitro Sciences.
authors.forename: Julie A
authors.initials: JA
authors.lastname: O'Brien
authors.affiliation: Psychiatry Research.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Magliaro
authors.affiliation: Central Pharmacology.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Uslaner
authors.affiliation: Central Pharmacology.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Huszar
authors.affiliation: Drug Metabolism.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Fillgrove
authors.affiliation: Drug Metabolism.
authors.forename: James H
authors.initials: JH
authors.lastname: Small
authors.affiliation: Drug Metabolism.
authors.forename: Cuyue
authors.initials: C
authors.lastname: Tang
authors.affiliation: Drug Metabolism.
authors.forename: Yuhsin
authors.initials: Y
authors.lastname: Kuo
authors.affiliation: Psychiatry Research.
authors.forename: Marlene A
authors.initials: MA
authors.lastname: Jacobson
keywords: GPCR; Oxazolobenzimidazoles; allosteric modulators; hyperlocomotion model; metabotropic glutamate 2 receptor; schizophrenia