Literature DB >> 24074843

Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety.

Andrew S Felts1, Alice L Rodriguez, Ryan D Morrison, Daryl F Venable, Jason T Manka, Brittney S Bates, Anna L Blobaum, Frank W Byers, J Scott Daniels, Colleen M Niswender, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte.   

Abstract

Development of SAR in an aryl ether series of mGlu5 NAMs leading to the identification of tool compound VU0409106 is described in this Letter. VU0409106 is a potent and selective negative allosteric modulator of mGlu5 that binds at the known allosteric binding site and demonstrates good CNS exposure following intraperitoneal dosing in mice. VU0409106 also proved efficacious in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlu5 antagonists as well as clinically efficacious anxiolytics.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Allosteric modulator; Anxiety; CNS; Glutamate; mGlu(5)

Mesh：

Substances：

Year:  2013        PMID： 24074843      PMCID： PMC3846293          DOI： 10.1016/j.bmcl.2013.09.001

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


  69 in total

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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
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Journal:  ACS Chem Biol       Date:  2008-07-25       Impact factor: 5.100

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

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4.  AFQ056 treatment of levodopa-induced dyskinesias: results of 2 randomized controlled trials.

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5.  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

6.  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

7.  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

8.  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

9.  Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice.

Authors:  Aubin Michalon; Michael Sidorov; Theresa M Ballard; Laurence Ozmen; Will Spooren; Joseph G Wettstein; Georg Jaeschke; Mark F Bear; Lothar Lindemann
Journal:  Neuron       Date:  2012-04-12       Impact factor: 17.173

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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  15 in total

1.  Partial mGlu₅ Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects.

Authors:  Robert W Gould; Russell J Amato; Michael Bubser; Max E Joffe; Michael T Nedelcovych; Analisa D Thompson; Hilary H Nickols; Johannes P Yuh; Xiaoyan Zhan; Andrew S Felts; Alice L Rodriguez; Ryan D Morrison; Frank W Byers; Jerri M Rook; John S Daniels; Colleen M Niswender; P Jeffrey Conn; Kyle A Emmitte; Craig W Lindsley; Carrie K Jones
Journal:  Neuropsychopharmacology       Date:  2015-08-28       Impact factor: 7.853

2.  Discovery of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5.

Authors:  Andrew S Felts; Alice L Rodriguez; Ryan D Morrison; Anna L Blobaum; Frank W Byers; J Scott Daniels; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2018-04-22       Impact factor: 2.823

3.  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

4.  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

5.  Relationship between in vivo receptor occupancy and efficacy of metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro binding profiles.

Authors:  Jerri M Rook; Mohammed N Tantawy; Mohammad S Ansari; Andrew S Felts; Shaun R Stauffer; Kyle A Emmitte; Robert M Kessler; Colleen M Niswender; J Scott Daniels; Carrie K Jones; Craig W Lindsley; P Jeffrey Conn
Journal:  Neuropsychopharmacology       Date:  2014-09-22       Impact factor: 7.853

6.  Discovery of imidazo[1,2-a]-, [1,2,4]triazolo[4,3-a]-, and [1,2,4]triazolo[1,5-a]pyridine-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5.

Authors:  Andrew S Felts; Alice L Rodriguez; Ryan D Morrison; Katrina A Bollinger; Daryl F Venable; Anna L Blobaum; Frank W Byers; Analisa Thompson Gray; J Scott Daniels; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2017-09-20       Impact factor: 2.823

7.  Discovery of 4-alkoxy-6-methylpicolinamide negative allosteric modulators of metabotropic glutamate receptor subtype 5.

Authors:  Andrew S Felts; Katrina A Bollinger; Christopher J Brassard; Alice L Rodriguez; Ryan D Morrison; J Scott Daniels; Anna L Blobaum; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; Kyle A Emmitte; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2018-11-10       Impact factor: 2.823

Review 8.  Therapeutic potential of targeting glutamate receptors in Parkinson's disease.

Authors:  Clare Finlay; Susan Duty
Journal:  J Neural Transm (Vienna)       Date:  2014-02-21       Impact factor: 3.575

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.  Discovery of a Selective and CNS Penetrant Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 3 with Antidepressant and Anxiolytic Activity in Rodents.

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Journal:  J Med Chem       Date:  2015-09-10       Impact factor: 7.446
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