title: Rational design, synthesis, and structure-activity relationship of benzoxazolones: new potent mglu5 receptor antagonists based on the fenobam structure.
abstract: A novel class of potent and stable mGlu5 receptor antagonists was developed by combining information from a high-throughput screening campaign with the structure of the known anxiolytic fenobam. Representative compounds from this class show favorable pharmacokinetic properties and are active in an in vivo model of anxiety.
authors.affiliation: Pharmaceutical Division, Discovery Research, F. Hoffmann-La Roche Ltd,CH-4070 Basel, Switzerland. Simona_m.ceccarelli@roche.com
authors.forename: Simona M
authors.initials: SM
authors.lastname: Ceccarelli
authors.forename: Georg
authors.initials: G
authors.lastname: Jaeschke
authors.forename: Bernd
authors.initials: B
authors.lastname: Buettelmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Huwyler
authors.forename: Sabine
authors.initials: S
authors.lastname: Kolczewski
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Peters
authors.forename: Eric
authors.initials: E
authors.lastname: Prinssen
authors.forename: Richard
authors.initials: R
authors.lastname: Porter
authors.forename: Will
authors.initials: W
authors.lastname: Spooren
authors.forename: Eric
authors.initials: E
authors.lastname: Vieira
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001007:Anxiety / Q000188:drug therapy; D001583:Benzoxazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007093:Imidazoles / Q000737:chemistry; D023421:Models, Animal; D010599:Pharmacokinetics; D011485:Protein Binding; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D001583:Benzoxazoles; D007093:Imidazoles; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C032794:fenobam; C017057:benzoxazolone