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.
MeSH terms
-
Animals
-
Anti-Anxiety Agents / chemical synthesis*
-
Anti-Anxiety Agents / chemistry
-
Anti-Anxiety Agents / pharmacokinetics
-
Anti-Anxiety Agents / pharmacology
-
Anxiety
-
Disease Models, Animal
-
Excitatory Amino Acid Antagonists / chemical synthesis
-
Excitatory Amino Acid Antagonists / chemistry
-
Excitatory Amino Acid Antagonists / pharmacology*
-
Kinetics
-
Models, Molecular
-
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
Substances
-
Anti-Anxiety Agents
-
Excitatory Amino Acid Antagonists
-
Pyridines
-
Receptor, Metabotropic Glutamate 5
-
Receptors, Metabotropic Glutamate
-
Thiazoles