Abstract
A series of 1,5-disubstituted pyridones was identified as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2) via high throughput screening (HTS). Subsequent SAR exploration led to the identification of several compounds with improved in vitro activity. Lead compound 8 was further profiled and found to attenuate the increase in PCP induced locomotor activity in mice.
Keywords:
PAM; allosteric; glutamate; mGluR2; metabotropic; modulators.
MeSH terms
-
Allosteric Regulation
-
Amino Acids / chemistry
-
Amino Acids / pharmacology*
-
Animals
-
Bridged Bicyclo Compounds / chemistry
-
Bridged Bicyclo Compounds / pharmacology*
-
Drug Evaluation, Preclinical
-
Drug Stability
-
Excitatory Amino Acid Agonists / chemistry
-
Excitatory Amino Acid Agonists / classification
-
Excitatory Amino Acid Agonists / pharmacology*
-
Humans
-
Hydrophobic and Hydrophilic Interactions
-
Mice
-
Molecular Structure
-
Motor Activity / drug effects
-
Pyridines / chemistry
-
Pyridines / pharmacology*
-
Pyridones / chemistry
-
Pyridones / classification
-
Pyridones / isolation & purification
-
Pyridones / pharmacology*
-
Receptors, Metabotropic Glutamate / agonists*
-
Recombinant Proteins / drug effects
-
Structure-Activity Relationship
-
Sulfonamides / chemistry
-
Sulfonamides / pharmacology*
Substances
-
Amino Acids
-
Bridged Bicyclo Compounds
-
Excitatory Amino Acid Agonists
-
LY 2140023
-
N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine
-
Pyridines
-
Pyridones
-
Receptors, Metabotropic Glutamate
-
Recombinant Proteins
-
Sulfonamides
-
metabotropic glutamate receptor 2
-
eglumetad