Literature DB >> 20598884

3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats.

Andrew S Felts1, Stacey R Lindsley, Jeffrey P Lamb, Alice L Rodriguez, Usha N Menon, Satyawan Jadhav, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte.   

Abstract

Development of SAR in a 3-cyano-5-fluoro-N-arylbenzamide series of non-competitive antagonists of mGlu(5) using a functional cell-based assay is described in this Letter. Further characterization of selected potent compounds in in vitro assays designed to measure their metabolic stability and protein binding is also presented. Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples. Copyright 2010 Elsevier Ltd. All rights reserved.

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Year:  2010        PMID： 20598884      PMCID： PMC2905502          DOI： 10.1016/j.bmcl.2010.06.064

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  45 in total

1.  Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice.

Authors:  C Chiamulera; M P Epping-Jordan; A Zocchi; C Marcon; C Cottiny; S Tacconi; M Corsi; F Orzi; F Conquet
Journal:  Nat Neurosci       Date:  2001-09       Impact factor: 24.884

2.  Development of a custom high-throughput preparative liquid chromatography/mass spectrometer platform for the preparative purification and analytical analysis of compound libraries.

Authors:  William Leister; Kimberly Strauss; David Wisnoski; Zhijian Zhao; Craig Lindsley
Journal:  J Comb Chem       Date:  2003 May-Jun

3.  Attenuation of behavioral effects of cocaine by the Metabotropic Glutamate Receptor 5 Antagonist 2-Methyl-6-(phenylethynyl)-pyridine in squirrel monkeys: comparison with dizocilpine.

Authors:  Buyean Lee; Donna M Platt; James K Rowlett; Adepero S Adewale; Roger D Spealman
Journal:  J Pharmacol Exp Ther       Date:  2004-11-18       Impact factor: 4.030

4.  Anxiolytic-like effects of mGlu1 and mGlu5 receptor antagonists in rats.

Authors:  Małgorzata Pietraszek; Ilia Sukhanov; Piotr Maciejak; Janusz Szyndler; Andreas Gravius; Aleksandra Wisłowska; Adam Płaźnik; Anton Y Bespalov; Wojciech Danysz
Journal:  Eur J Pharmacol       Date:  2005-04-19       Impact factor: 4.432

5.  Transient lower esophageal sphincter relaxations in dogs are inhibited by a metabotropic glutamate receptor 5 antagonist.

Authors:  Jörgen Jensen; Anders Lehmann; Anna Uvebrant; Anita Carlsson; Gunilla Jerndal; Karolina Nilsson; Claudine Frisby; L Ashley Blackshaw; Jan P Mattsson
Journal:  Eur J Pharmacol       Date:  2005-09-05       Impact factor: 4.432

6.  Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling.

Authors:  Aleksandra Klodzinska; Ewa Tatarczyńska; Ewa Chojnacka-Wójcik; Gabriel Nowak; Nicholas D P Cosford; Andrzej Pilc
Journal:  Neuropharmacology       Date:  2004-09       Impact factor: 5.250

7.  The mGluR5 antagonist MPEP reduces the conditioned rewarding effects of cocaine but not other drugs of abuse.

Authors:  Andrew J McGeehan; M Foster Olive
Journal:  Synapse       Date:  2003-03       Impact factor: 2.562

8.  Cue-induced reinstatement of alcohol-seeking behavior is associated with increased ERK1/2 phosphorylation in specific limbic brain regions: blockade by the mGluR5 antagonist MPEP.

Authors:  Jason P Schroeder; Marina Spanos; Jennie R Stevenson; Joyce Besheer; Michael Salling; Clyde W Hodge
Journal:  Neuropharmacology       Date:  2008-07-04       Impact factor: 5.250

9.  Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5.

Authors:  Andrew S Felts; Sam A Saleh; Uyen Le; Alice L Rodriguez; C David Weaver; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2009-10-09       Impact factor: 2.823

10.  A proof-of-concept study evaluating the effect of ADX10059, a metabotropic glutamate receptor-5 negative allosteric modulator, on acid exposure and symptoms in gastro-oesophageal reflux disease.

Authors:  C Keywood; M Wakefield; J Tack
Journal:  Gut       Date:  2009-05-20       Impact factor: 23.059
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  17 in total

1.  Discovery of 2-(2-benzoxazoyl amino)-4-aryl-5-cyanopyrimidine as negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu₅): from an artificial neural network virtual screen to an in vivo tool compound.

Authors:  Ralf Mueller; Eric S Dawson; Jens Meiler; Alice L Rodriguez; Brian A Chauder; Brittney S Bates; Andrew S Felts; Jeffrey P Lamb; Usha N Menon; Sataywan B Jadhav; Alexander S Kane; Carrie K Jones; Karen J Gregory; Colleen M Niswender; P Jeffrey Conn; Christopher M Olsen; Danny G Winder; Kyle A Emmitte; Craig W Lindsley
Journal:  ChemMedChem       Date:  2012-01-20       Impact factor: 3.466

2.  Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.

Authors:  Jeffrey P Lamb; Darren W Engers; Colleen M Niswender; Alice L Rodriguez; Daryl F Venable; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2010-12-03       Impact factor: 2.823

3.  Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation.

Authors:  Karen J Gregory; P Jeffrey Conn
Journal:  Mol Pharmacol       Date:  2015-03-25       Impact factor: 4.436

4.  Kinetic and system bias as drivers of metabotropic glutamate receptor 5 allosteric modulator pharmacology.

Authors:  Kathy Sengmany; Shane D Hellyer; Sabine Albold; Taide Wang; P Jeffrey Conn; Lauren T May; Arthur Christopoulos; Katie Leach; Karen J Gregory
Journal:  Neuropharmacology       Date:  2019-02-11       Impact factor: 5.250

5.  Identification of specific ligand-receptor interactions that govern binding and cooperativity of diverse modulators to a common metabotropic glutamate receptor 5 allosteric site.

Authors:  Karen J Gregory; Elizabeth D Nguyen; Chrysa Malosh; Jeffrey L Mendenhall; Jessica Z Zic; Brittney S Bates; Meredith J Noetzel; Emma F Squire; Eric M Turner; Jerri M Rook; Kyle A Emmitte; Shaun R Stauffer; Craig W Lindsley; Jens Meiler; P Jeffrey Conn
Journal:  ACS Chem Neurosci       Date:  2014-02-26       Impact factor: 4.418

6.  A novel class of succinimide-derived negative allosteric modulators of metabotropic glutamate receptor subtype 1 provides insight into a disconnect in activity between the rat and human receptors.

Authors:  Hyekyung P Cho; Darren W Engers; Daryl F Venable; Colleen M Niswender; Craig W Lindsley; P Jeffrey Conn; Kyle A Emmitte; Alice L Rodriguez
Journal:  ACS Chem Neurosci       Date:  2014-05-15       Impact factor: 4.418

7.  Recent advances in the design and development of novel negative allosteric modulators of mGlu(5).

Authors:  Kyle A Emmitte
Journal:  ACS Chem Neurosci       Date:  2011-08-17       Impact factor: 4.418

8.  (3-Cyano-5-fluorophenyl)biaryl negative allosteric modulators of mGlu(5): Discovery of a new tool compound with activity in the OSS mouse model of addiction.

Authors:  Craig W Lindsley; Brittney S Bates; Usha N Menon; Satyawan B Jadhav; Alexander S Kane; Carrie K Jones; Alice L Rodriguez; P Jeffrey Conn; Christopher M Olsen; Danny G Winder; Kyle A Emmitte
Journal:  ACS Chem Neurosci       Date:  2011-08-17       Impact factor: 4.418

9.  Discovery of VU0431316: a negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety.

Authors:  Brittney S Bates; Alice L Rodriguez; Andrew S Felts; Ryan D Morrison; Daryl F Venable; Anna L Blobaum; Frank W Byers; Kera P Lawson; J Scott Daniels; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2014-06-11       Impact factor: 2.823

10.  Substituted 1-Phenyl-3-(pyridin-2-yl)urea negative allosteric modulators of mGlu5: discovery of a new tool compound VU0463841 with activity in rat models of cocaine addiction.

Authors:  Russell J Amato; Andrew S Felts; Alice L Rodriguez; Daryl F Venable; Ryan D Morrison; Frank W Byers; J Scott Daniels; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Carrie K Jones; Kyle A Emmitte
Journal:  ACS Chem Neurosci       Date:  2013-05-29       Impact factor: 4.418
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