Rational design, synthesis, and structure-activity relationship of benzoxazolones: new potent mglu5 receptor antagonists based on the fenobam structure.
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.
Ceccarelli
Simona M
SM
Pharmaceutical Division, Discovery Research, F. Hoffmann-La Roche Ltd,CH-4070 Basel, Switzerland. Simona_m.ceccarelli@roche.com
Jaeschke
Georg
G
Buettelmann
Bernd
B
Huwyler
Jörg
J
Kolczewski
Sabine
S
Peters
Jens-Uwe
JU
Prinssen
Eric
E
Porter
Richard
R
Spooren
Will
W
Vieira
Eric
E
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
D014151:Anti-Anxiety Agents; D001583:Benzoxazoles; D007093:Imidazoles; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C032794:fenobam; C017057:benzoxazolone