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

Graphic 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...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2004-08, Vol.14 (15), p.3993-3996
Hauptverfasser:	Roppe, Jeffrey R, Wang, Bowei, Huang, Dehua, Tehrani, Lida, Kamenecka, Theodore, Schweiger, Edwin J, Anderson, Jeffery J, Brodkin, Jesse, Jiang, Xiaohui, Cramer, Merryl, Chung, Janice, Reyes-Manalo, Grace, Munoz, Benito, Cosford, Nicholas D.P
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Anti-Anxiety Agents - chemical synthesis Anti-Anxiety Agents - chemistry Anti-Anxiety Agents - pharmacokinetics Anti-Anxiety Agents - pharmacology Anxiety Biological and medical sciences Disease Models, Animal Excitatory Amino Acid Antagonists - chemical synthesis Excitatory Amino Acid Antagonists - chemistry Excitatory Amino Acid Antagonists - pharmacology Kinetics Medical sciences Metabotropic glutamate receptor mGluR mGluR5 Miscellaneous Models, Molecular MPEP MTEP Neuropharmacology Pharmacology. Drug treatments Psycholeptics: tranquillizer, neuroleptic Psychology. Psychoanalysis. Psychiatry Psychopharmacology Pyridines - chemical synthesis Pyridines - chemistry Pyridines - pharmacokinetics Pyridines - pharmacology Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate - drug effects Receptors, Metabotropic Glutamate - physiology Structure-Activity Relationship Thiazoles - chemical synthesis Thiazoles - chemistry Thiazoles - pharmacokinetics Thiazoles - pharmacology
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Zusammenfassung:	Graphic 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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2004.05.037