title: Arylmethoxypyridines as novel, potent and orally active mGlu5 receptor antagonists.
abstract: Optimisation of affinity, chemical stability, metabolic stability and solubility led from a chemically labile HTS hit 1 to mGlu5 receptor antagonists (24-26) with high affinity for the allosteric MPEP binding site, improved microsomal metabolic stability and anxiolytic-like activity in vivo as assessed by the Vogel conflict drinking test.
authors.affiliation: Pharma Division, Discovery Chemistry, F. Hoffman-La Roche Ltd, CH-4070 Basel, Switzerland.
authors.forename: Bernd
authors.initials: B
authors.lastname: Büttelmann
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Peters
authors.forename: Simona
authors.initials: S
authors.lastname: Ceccarelli
authors.forename: Sabine
authors.initials: S
authors.lastname: Kolczewski
authors.forename: Eric
authors.initials: E
authors.lastname: Vieira
authors.forename: Eric P
authors.initials: EP
authors.lastname: Prinssen
authors.forename: Will
authors.initials: W
authors.lastname: Spooren
authors.forename: Franz
authors.initials: F
authors.lastname: Schuler
authors.forename: Jörg
authors.initials: J
authors.lastname: Huwyler
authors.forename: Richard H P
authors.initials: RH
authors.lastname: Porter
authors.forename: Georg
authors.initials: G
authors.lastname: Jaeschke
mesh_terms: D000284:Administration, Oral; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate