title: 5-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-2,3'-bipyridine: a highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist with anxiolytic activity.
abstract: Structure-activity relationship studies leading to the discovery of a new, orally active mGlu5 receptor antagonist are described. The title compound, 5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-2,3'-bipyridine, is highly potent in vitro, has good in vivo receptor occupancy, and is efficacious in the rat fear-potentiated startle model of anxiety following oral dosing.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, San Diego, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. jeffrey_roppe@merck.com
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Roppe
authors.forename: Bowei
authors.initials: B
authors.lastname: Wang
authors.forename: Dehua
authors.initials: D
authors.lastname: Huang
authors.forename: Lida
authors.initials: L
authors.lastname: Tehrani
authors.forename: Theodore
authors.initials: T
authors.lastname: Kamenecka
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Schweiger
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Anderson
authors.forename: Jesse
authors.initials: J
authors.lastname: Brodkin
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Jiang
authors.forename: Merryl
authors.initials: M
authors.lastname: Cramer
authors.forename: Janice
authors.initials: J
authors.lastname: Chung
authors.forename: Grace
authors.initials: G
authors.lastname: Reyes-Manalo
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
authors.forename: Nicholas D P
authors.initials: ND
authors.lastname: Cosford
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001007:Anxiety; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles