Synthesis and biological evaluation of fenobam analogs as mGlu5 receptor antagonists

Georg Jaeschke; Richard Porter; Bernd Büttelmann; Simona M Ceccarelli; Wolfgang Guba; Bernd Kuhn; Sabine Kolczewski; Jörg Huwyler; Vincent Mutel; Jens-Uwe Peters; Theresa Ballard; Eric Prinssen; Eric Vieira; Jürgen Wichmann; Will Spooren

doi:10.1016/j.bmcl.2006.12.033

Synthesis and biological evaluation of fenobam analogs as mGlu5 receptor antagonists

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1307-11. doi: 10.1016/j.bmcl.2006.12.033. Epub 2006 Dec 15.

Authors

Georg Jaeschke¹, Richard Porter, Bernd Büttelmann, Simona M Ceccarelli, Wolfgang Guba, Bernd Kuhn, Sabine Kolczewski, Jörg Huwyler, Vincent Mutel, Jens-Uwe Peters, Theresa Ballard, Eric Prinssen, Eric Vieira, Jürgen Wichmann, Will Spooren

Affiliation

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

PMID: 17196387
DOI: 10.1016/j.bmcl.2006.12.033

Abstract

Optimization of affinity and microsomal stability led to identification of the potent, metabolically stable fenobam analog 4l. Robust in vivo efficacy of 4l was demonstrated in four different models of anxiety. Additionally, a ligand based pharmacophore alignment of fenobam and MPEP is proposed.

MeSH terms

Animals
Anti-Anxiety Agents / chemical synthesis
Drug Design
Humans
Imidazoles / chemistry*
Imidazoles / pharmacology*
Ligands
Pyridines / chemistry
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Anti-Anxiety Agents
Imidazoles
Ligands
Pyridines
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate
fenobam
6-methyl-2-(phenylethynyl)pyridine