Literature DB >> 22030026

Synthesis and SAR of a novel metabotropic glutamate receptor 4 (mGlu4) antagonist: unexpected 'molecular switch' from a closely related mGlu4 positive allosteric modulator.

Thomas Utley1, Dustin Haddenham, James M Salovich, Rocio Zamorano, Paige N Vinson, Craig W Lindsley, Corey R Hopkins, Colleen M Niswender.   

Abstract

Herein we report the discovery and SAR of a novel antagonist of metabotropic glutamate receptor 4 (mGlu(4)). The antagonist was discovered via a molecular switch from a closely related mGlu(4) positive allosteric modulator (PAM). This antagonist (VU0448383) displays an IC(50) value of 8.2±0.4 μM and inhibits an EC(80) glutamate response by 63.1±6.6%. Copyright Â
© 2011 Elsevier Ltd. All rights reserved.

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Year:  2011        PMID： 22030026      PMCID： PMC3319082          DOI： 10.1016/j.bmcl.2011.09.131

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


  8 in total

1.  Chemical switch of a metabotropic glutamate receptor 2 silent allosteric modulator into dual metabotropic glutamate receptor 2/3 negative/positive allosteric modulators.

Authors:  Stephan Schann; Stanislas Mayer; Christel Franchet; Mélanie Frauli; Edith Steinberg; Mireille Thomas; Luc Baron; Pascal Neuville
Journal:  J Med Chem       Date:  2010-11-24       Impact factor: 7.446

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.  A novel assay of Gi/o-linked G protein-coupled receptor coupling to potassium channels provides new insights into the pharmacology of the group III metabotropic glutamate receptors.

Authors:  Colleen M Niswender; Kari A Johnson; Qingwei Luo; Jennifer E Ayala; Caroline Kim; P Jeffrey Conn; C David Weaver
Journal:  Mol Pharmacol       Date:  2008-01-02       Impact factor: 4.436

Review 4.  "Molecular switches" on mGluR allosteric ligands that modulate modes of pharmacology.

Authors:  Michael R Wood; Corey R Hopkins; John T Brogan; P Jeffrey Conn; Craig W Lindsley
Journal:  Biochemistry       Date:  2011-03-04       Impact factor: 3.162

Review 5.  mGluR4-positive allosteric modulation as potential treatment for Parkinson's disease.

Authors:  Corey R Hopkins; Craig W Lindsley; Colleen M Niswender
Journal:  Future Med Chem       Date:  2009-06       Impact factor: 3.808

Review 6.  Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia.

Authors:  P Jeffrey Conn; Craig W Lindsley; Carrie K Jones
Journal:  Trends Pharmacol Sci       Date:  2008-12-06       Impact factor: 14.819

7.  Discovery of molecular switches that modulate modes of metabotropic glutamate receptor subtype 5 (mGlu5) pharmacology in vitro and in vivo within a series of functionalized, regioisomeric 2- and 5-(phenylethynyl)pyrimidines.

Authors:  Sameer Sharma; Jeffrey Kedrowski; Jerri M Rook; Randy L Smith; Carrie K Jones; Alice L Rodriguez; P Jeffrey Conn; Craig W Lindsley
Journal:  J Med Chem       Date:  2009-07-23       Impact factor: 7.446

Review 8.  Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders.

Authors:  P Jeffrey Conn; Arthur Christopoulos; Craig W Lindsley
Journal:  Nat Rev Drug Discov       Date:  2009-01       Impact factor: 84.694
  8 in total
  8 in total

Review 1.  Drugs for allosteric sites on receptors.

Authors:  Cody J Wenthur; Patrick R Gentry; Thomas P Mathews; Craig W Lindsley
Journal:  Annu Rev Pharmacol Toxicol       Date:  2013-10-02       Impact factor: 13.820

Review 2.  Allosteric modulation of Class C GPCRs: a novel approach for the treatment of CNS disorders.

Authors:  Darren W Engers; Craig W Lindsley
Journal:  Drug Discov Today Technol       Date:  2013

3.  Synthesis and SAR of substituted pyrazolo[1,5-a]quinazolines as dual mGlu(2)/mGlu(3) NAMs.

Authors:  Cody J Wenthur; Ryan D Morrison; J Scott Daniels; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2014-04-20       Impact factor: 2.823

Review 4.  Development of allosteric modulators of GPCRs for treatment of CNS disorders.

Authors:  Hilary Highfield Nickols; P Jeffrey Conn
Journal:  Neurobiol Dis       Date:  2013-09-27       Impact factor: 5.996

5.  Synthesis and Biological Characterization of a Series of 2-Sulfonamidebenzamides as Allosteric Modulators of MrgX1.

Authors:  Swagat Sharma; Qi Peng; Anish K Vadukoot; Christopher D Aretz; Aaron A Jensen; Alexander I Wallick; Xinzhong Dong; Corey R Hopkins
Journal:  ACS Med Chem Lett       Date:  2022-04-19       Impact factor: 4.632

Review 6.  Recent advances in the medicinal chemistry of group II and group III mGlu receptors.

Authors:  Chaobin Jin; Shutao Ma
Journal:  Medchemcomm       Date:  2017-01-13       Impact factor: 3.597

Review 7.  2013 Philip S. Portoghese Medicinal Chemistry Lectureship: drug discovery targeting allosteric sites.

Authors:  Craig W Lindsley
Journal:  J Med Chem       Date:  2014-09-15       Impact factor: 7.446

Review 8.  Allosteric Molecular Switches in Metabotropic Glutamate Receptors.

Authors:  Zoltán Orgován; György G Ferenczy; György M Keserű
Journal:  ChemMedChem       Date:  2020-08-25       Impact factor: 3.466
  8 in total

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