title: Rational design of 7-arylquinolines as non-competitive metabotropic glutamate receptor subtype 5 antagonists.
abstract: Rational replacement of the alkyne linker of mGluR5 antagonist MPEP gave 7-arylquinolines. SAR optimization gave an orally active compound with high affinity for the MPEP binding site.
authors.affiliation: Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. Jared.Milbank@Pfizer.com
authors.forename: Jared B J
authors.initials: JB
authors.lastname: Milbank
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Knauer
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Augelli-Szafran
authors.forename: Annette T
authors.initials: AT
authors.lastname: Sakkab-Tan
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Lin
authors.forename: Koji
authors.initials: K
authors.lastname: Yamagata
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Hoffman
authors.forename: Nian
authors.initials: N
authors.lastname: Zhuang
authors.forename: John
authors.initials: J
authors.lastname: Thomas
authors.forename: Paul
authors.initials: P
authors.lastname: Galatsis
authors.forename: John A
authors.initials: JA
authors.lastname: Wendt
authors.forename: John W
authors.initials: JW
authors.lastname: Mickelson
authors.forename: Roy D
authors.initials: RD
authors.lastname: Schwarz
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Kinsora
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lotarski
authors.forename: Korana
authors.initials: K
authors.lastname: Stakich
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Gillespie
authors.forename: Wing W
authors.initials: WW
authors.lastname: Lam
authors.forename: Abdul E
authors.initials: AE
authors.lastname: Mutlib
mesh_terms: D015195:Drug Design; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D011804:Quinolines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine