Phenyl-tetrazolyl Acetophenones:  Discovery of Positive Allosteric Potentiatiors for the Metabotropic Glutamate 2 Receptor

Herein we disclose the discovery of a new class of positive allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2), phenyl-tetrazolyl acetophenones, e.g. 1-(2-hydroxy-3-propyl-4-{4-[4-(2H-tetrazol-5-yl)phenoxy]butoxy}phenyl) ethanone (4). These potentiators were shown to have no ef...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2004-08, Vol.47 (18), p.4595-4599
Main Authors: Pinkerton, Anthony B, Vernier, Jean-Michel, Schaffhauser, Hervé, Rowe, Blake A, Campbell, Una C, Rodriguez, Dana E, Lorrain, Daniel S, Baccei, Christopher S, Daggett, Lorrie P, Bristow, Linda J
Format: Article
Language:English
Subjects:
Acetophenones - chemical synthesis
Acetophenones - pharmacology
Allosteric Regulation
Animals
Behavior - drug effects
Biological and medical sciences
Brain - metabolism
Dose-Response Relationship, Drug
Glutamatergic system (aspartate and other excitatory aminoacids)
Glutamic Acid - pharmacology
Hyperkinesis - drug therapy
Medical sciences
Miscellaneous
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Norepinephrine - metabolism
Pharmacology. Drug treatments
Rats
Receptors, Metabotropic Glutamate - agonists
Schizophrenia - drug therapy
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Herein we disclose the discovery of a new class of positive allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2), phenyl-tetrazolyl acetophenones, e.g. 1-(2-hydroxy-3-propyl-4-{4-[4-(2H-tetrazol-5-yl)phenoxy]butoxy}phenyl) ethanone (4). These potentiators were shown to have no effect in the absence of glutamate as well as no effect at mGlu3 or the other mGlu receptors. The compounds were also evaluated in rodent models with potential relevance for schizophrenia, and 4 was shown to have activity in the inhibition of ketamine-induced norepinephrine release and ketamine-induced hyperactivity. This represents the first example of the efficacy of mGlu2 receptor potentiators in these models.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm040088h