title: Discovery of novel heteroarylazoles that are metabotropic glutamate subtype 5 receptor antagonists with anxiolytic activity.
abstract: The highly potent, selective, and brain-penetrant metabotropic glutamate subtype 5 (mGlu5) receptor antagonists 3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile (47) and 3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile (48) are reported. Compound 47 is active in the rat fear-potentiated startle (FPS) model of anxiety with ED(50) = 5.4 mg/kg (po) when dosed acutely. In this model the anxiolytic effects of 47 rapidly tolerate on repeated dosing.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Roppe
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Smith
authors.forename: Dehua
authors.initials: D
authors.lastname: Huang
authors.forename: Lida
authors.initials: L
authors.lastname: Tehrani
authors.forename: Bowei
authors.initials: B
authors.lastname: Wang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Anderson
authors.forename: Jesse
authors.initials: J
authors.lastname: Brodkin
authors.forename: Janice
authors.initials: J
authors.lastname: Chung
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Jiang
authors.forename: Christopher
authors.initials: C
authors.lastname: King
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Varney
authors.forename: Petpiboon
authors.initials: P
authors.lastname: Prasit
authors.forename: Nicholas D P
authors.initials: ND
authors.lastname: Cosford
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate