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Discovery of 2‐(2‐Benzoxazoyl amino)‐4‐Aryl‐5‐Cyanopyrimidine as Negative Allosteric Modulators (NAMs) of Metabotropic Glutamate Receptor 5 (mGlu 5 ): From an Artificial Neural Network Virtual Screen to an In Vivo Tool Compound
Author(s) -
Mueller Ralf,
Dawson Eric S.,
Meiler Jens,
Rodriguez Alice L.,
Chauder Brian A.,
Bates Brittney S.,
Felts Andrew S.,
Lamb Jeffrey P.,
Me Usha N.,
Jadhav Sataywan B.,
Kane Alexander S.,
Jones Carrie K.,
Gregory Karen J.,
Niswender Colleen M.,
Conn P. Jeffrey,
Olsen Christopher M.,
Winder Danny G.,
Emmitte Kyle A.,
Lindsley Craig W.
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100510
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 5 , allosteric regulation , metabotropic glutamate receptor 2 , virtual screening , artificial neural network , metabotropic glutamate receptor 1 , metabotropic receptor , glutamate receptor , metabotropic glutamate receptor 7 , chemistry , drug discovery , computational biology , neuroscience , computer science , artificial intelligence , receptor , biochemistry , biology
From ANNs to NAMs! Data from an experimental metabotropic glutamate receptor 5 (mGlu 5 ) high‐throughput screen (HTS) were employed to train artificial neural networks (ANNs) based on 345 confirmed negative allosteric modulators (NAMs) and 155 774 inactive compounds. This effort identified two potent mGlu 5 NAMs with a unique chemotype. Optimization afforded a tool compound (shown), active in mouse models of anxiety and addiction.