title: Synthesis and biological evaluation of fenobam analogs as mGlu5 receptor antagonists.
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.
authors.affiliation: Pharmaceutical Division, Discovery Research, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. georg.jaeschke@roche.com
authors.forename: Georg
authors.initials: G
authors.lastname: Jaeschke
authors.forename: Richard
authors.initials: R
authors.lastname: Porter
authors.forename: Bernd
authors.initials: B
authors.lastname: Büttelmann
authors.forename: Simona M
authors.initials: SM
authors.lastname: Ceccarelli
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Guba
authors.forename: Bernd
authors.initials: B
authors.lastname: Kuhn
authors.forename: Sabine
authors.initials: S
authors.lastname: Kolczewski
authors.forename: Jörg
authors.initials: J
authors.lastname: Huwyler
authors.forename: Vincent
authors.initials: V
authors.lastname: Mutel
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Peters
authors.forename: Theresa
authors.initials: T
authors.lastname: Ballard
authors.forename: Eric
authors.initials: E
authors.lastname: Prinssen
authors.forename: Eric
authors.initials: E
authors.lastname: Vieira
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wichmann
authors.forename: Will
authors.initials: W
authors.lastname: Spooren
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D008024:Ligands; D011725:Pyridines / Q000737:chemistry; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D007093:Imidazoles; D008024:Ligands; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C032794:fenobam; C121465:6-methyl-2-(phenylethynyl)pyridine