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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.

SUBMITTER: Garbaccio RM

PROVIDER: S-EPMC4007895 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other

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Discovery of Oxazolobenzimidazoles as Positive Allosteric Modulators for the mGluR2 Receptor.

Garbaccio Robert M RM Brnardic Edward J EJ Fraley Mark E ME Hartman George D GD Hutson Pete H PH O'Brien Julie A JA Magliaro Brian C BC Uslaner Jason M JM Huszar Sarah L SL Fillgrove Kerry L KL Small James H JH Tang Cuyue C Kuo Yuhsin Y Jacobson Marlene A MA

ACS medicinal chemistry letters 20100712 8

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 schiz ...[more]

PMID: 24900224

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