Literature DB >> 24969015

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

Brittney S Bates1, Alice L Rodriguez1, Andrew S Felts1, Ryan D Morrison1, Daryl F Venable1, Anna L Blobaum1, Frank W Byers1, Kera P Lawson1, J Scott Daniels1, Colleen M Niswender1, Carrie K Jones2, P Jeffrey Conn1, Craig W Lindsley3, Kyle A Emmitte4.   

Abstract

Development of SAR in an aryl ether series of mGlu5 NAMs leading to the identification of pyrazine analog VU0431316 is described in this Letter. VU0431316 is a potent and selective non-competitive antagonist of mGlu5 that binds at a known allosteric binding site. VU0431316 demonstrates an attractive DMPK profile, including moderate clearance and good bioavailability in rats. Intraperitoneal (IP) dosing of VU0431316 in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlu5 antagonists and other anxiolytics, produced dose proportional effects.
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

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

Mesh：

Substances：

Year:  2014        PMID： 24969015      PMCID： PMC4090943          DOI： 10.1016/j.bmcl.2014.06.003

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


  68 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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Authors:  Thomas M Bridges; Craig W Lindsley
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.

Authors:  Andrew S Felts; 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
Journal:  Bioorg Med Chem Lett       Date:  2010-06-15       Impact factor: 2.823

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

Authors:  Daniela Berg; Jana Godau; Claudia Trenkwalder; Karla Eggert; Iiona Csoti; Alexander Storch; Heiko Huber; Monica Morelli-Canelo; Maria Stamelou; Vincent Ries; Martin Wolz; Christine Schneider; Thérèse Di Paolo; Fabrizio Gasparini; Sam Hariry; Marc Vandemeulebroecke; Walid Abi-Saab; Katy Cooke; Donald Johns; Baltazar Gomez-Mancilla
Journal:  Mov Disord       Date:  2011-04-11       Impact factor: 10.338

5.  Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator.

Authors:  Lei Zhang; Gayatri Balan; Gabriela Barreiro; Brian P Boscoe; Lois K Chenard; Julie Cianfrogna; Michelle M Claffey; Laigao Chen; Karen J Coffman; Susan E Drozda; Joshua R Dunetz; Kari R Fonseca; Paul Galatsis; Sarah Grimwood; John T Lazzaro; Jessica Y Mancuso; Emily L Miller; Matthew R Reese; Bruce N Rogers; Isao Sakurada; Marc Skaddan; Deborah L Smith; Antonia F Stepan; Patrick Trapa; Jamison B Tuttle; Patrick R Verhoest; Daniel P Walker; Ann S Wright; Margaret M Zaleska; Kenneth Zasadny; Christopher L Shaffer
Journal:  J Med Chem       Date:  2014-01-22       Impact factor: 7.446

6.  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

7.  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

8.  Room-temperature Pd-catalyzed amidation of aryl bromides using tert-butyl carbamate.

Authors:  Swapna Bhagwanth; Alex G Waterson; George M Adjabeng; Keith R Hornberger
Journal:  J Org Chem       Date:  2009-06-19       Impact factor: 4.354

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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  4 in total

1.  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

2.  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

3.  Computer-aided design of negative allosteric modulators of metabotropic glutamate receptor 5 (mGluR5): Comparative molecular field analysis of aryl ether derivatives.

Authors:  Chelliah Selvam; Ramasamy Thilagavathi; Balasubramanian Narasimhan; Pradeep Kumar; Brian C Jordan; Kasturi Ranganna
Journal:  Bioorg Med Chem Lett       Date:  2016-01-19       Impact factor: 2.823

4.  Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation.

Authors:  Andrew S Felts; Alice L Rodriguez; Anna L Blobaum; Ryan D Morrison; Brittney S Bates; Analisa Thompson Gray; Jerri M Rook; Mohammed N Tantawy; Frank W Byers; Sichen Chang; Daryl F Venable; Vincent B Luscombe; Gilles D Tamagnan; Colleen M Niswender; J Scott Daniels; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  J Med Chem       Date:  2017-05-31       Impact factor: 7.446
  4 in total

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