Rational design, synthesis, and structure-activity relationship of benzoxazolones: new potent mglu5 receptor antagonists based on the fenobam structure

Simona M Ceccarelli; Georg Jaeschke; Bernd Buettelmann; Jörg Huwyler; Sabine Kolczewski; Jens-Uwe Peters; Eric Prinssen; Richard Porter; Will Spooren; Eric Vieira

doi:10.1016/j.bmcl.2006.12.006

Rational design, synthesis, and structure-activity relationship of benzoxazolones: new potent mglu5 receptor antagonists based on the fenobam structure

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1302-6. doi: 10.1016/j.bmcl.2006.12.006. Epub 2006 Dec 15.

Authors

Simona M Ceccarelli¹, Georg Jaeschke, Bernd Buettelmann, Jörg Huwyler, Sabine Kolczewski, Jens-Uwe Peters, Eric Prinssen, Richard Porter, Will Spooren, Eric Vieira

Affiliation

¹ Pharmaceutical Division, Discovery Research, F. Hoffmann-La Roche Ltd,CH-4070 Basel, Switzerland. Simona_m.ceccarelli@roche.com

PMID: 17189691
DOI: 10.1016/j.bmcl.2006.12.006

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.

MeSH terms

Animals
Anti-Anxiety Agents / administration & dosage
Anti-Anxiety Agents / chemical synthesis*
Anti-Anxiety Agents / pharmacokinetics
Anxiety / drug therapy
Benzoxazoles / administration & dosage
Benzoxazoles / chemical synthesis*
Benzoxazoles / pharmacokinetics*
Drug Design
Drug Evaluation, Preclinical / methods
Imidazoles / chemistry
Models, Animal
Pharmacokinetics
Protein Binding
Rats
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Anti-Anxiety Agents
Benzoxazoles
Imidazoles
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate
fenobam
benzoxazolone