Literature DB >> 21295978

Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5.

Mu-Fa Zou1, Jianjing Cao, Alice L Rodriguez, P Jeffrey Conn, Amy Hauck Newman.   

Abstract

Based on SAR in the alkyne class of mGlu5 receptor negative allosteric modulators and a set of amide-based positive allosteric modulators, optimized substitution of the aryl 'b' ring was used to create substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides. Results from an mGlu5 receptor functional assay, using calcium fluorescence, revealed varying efficacies and potencies that provide evidence that subtle changes in compounds within a close structural class can have marked effects on functional activity including switches in modes of efficacy (i.e., negative to positive allosteric modulation). Published by Elsevier Ltd.

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Year:  2010        PMID： 21295978      PMCID： PMC3081927          DOI： 10.1016/j.bmcl.2010.12.110

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


  22 in total

1.  Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity.

Authors:  Alice L Rodriguez; Mark D Grier; Carrie K Jones; Elizabeth J Herman; Alexander S Kane; Randy L Smith; Richard Williams; Ya Zhou; Joy E Marlo; Emily L Days; Tasha N Blatt; Satyawan Jadhav; Usha N Menon; Paige N Vinson; Jerri M Rook; Shaun R Stauffer; Colleen M Niswender; Craig W Lindsley; C David Weaver; P Jeffrey Conn
Journal:  Mol Pharmacol       Date:  2010-10-05       Impact factor: 4.436

2.  The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester interact with overlapping binding pockets in the transmembrane region of group I metabotropic glutamate receptors.

Authors:  A Pagano; D Ruegg; S Litschig; N Stoehr; C Stierlin; M Heinrich; P Floersheim; L Prezèau; F Carroll; J P Pin; A Cambria; I Vranesic; P J Flor; F Gasparini; R Kuhn
Journal:  J Biol Chem       Date:  2000-10-27       Impact factor: 5.157

Review 3.  The metabotropic glutamate receptors: structure, activation mechanism and pharmacology.

Authors:  Jean-Philippe Pin; Francine Acher
Journal:  Curr Drug Targets CNS Neurol Disord       Date:  2002-06

4.  3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity.

Authors:  Nicholas D P Cosford; Lida Tehrani; Jeffrey Roppe; Edwin Schweiger; Nicholas D Smith; Jeffrey Anderson; Linda Bristow; Jesse Brodkin; Xiaohui Jiang; Ian McDonald; Sara Rao; Mark Washburn; Mark A Varney
Journal:  J Med Chem       Date:  2003-01-16       Impact factor: 7.446

Review 5.  Pharmacology and functions of metabotropic glutamate receptors.

Authors:  P J Conn; J P Pin
Journal:  Annu Rev Pharmacol Toxicol       Date:  1997       Impact factor: 13.820

6.  mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia.

Authors:  K Walker; A Reeve; M Bowes; J Winter; G Wotherspoon; A Davis; P Schmid; F Gasparini; R Kuhn; L Urban
Journal:  Neuropharmacology       Date:  2001       Impact factor: 5.250

7.  Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment.

Authors:  Michael J Marino; David L Williams; Julie A O'Brien; Ornella Valenti; Terrence P McDonald; Michelle K Clements; Ruiping Wang; Anthony G DiLella; J Fred Hess; Gene G Kinney; P Jeffrey Conn
Journal:  Proc Natl Acad Sci U S A       Date:  2003-10-30       Impact factor: 11.205

8.  Mutational analysis and molecular modeling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)-pyridine.

Authors:  Pari Malherbe; Nicole Kratochwil; Marie-Thérèse Zenner; Jenny Piussi; Catherine Diener; Claudia Kratzeisen; Christophe Fischer; Richard H P Porter
Journal:  Mol Pharmacol       Date:  2003-10       Impact factor: 4.436

9.  Anxiolytic-like activity of the mGluR5 antagonist MPEP: a comparison with diazepam and buspirone.

Authors:  Jesse Brodkin; Chris Busse; Stacey J Sukoff; Mark A Varney
Journal:  Pharmacol Biochem Behav       Date:  2002-09       Impact factor: 3.533

Review 10.  The ups and downs of addiction: role of metabotropic glutamate receptors.

Authors:  Paul J Kenny; Athina Markou
Journal:  Trends Pharmacol Sci       Date:  2004-05       Impact factor: 14.819
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  6 in total

Review 1.  Progress toward positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5).

Authors:  Shaun R Stauffer
Journal:  ACS Chem Neurosci       Date:  2011-06-27       Impact factor: 4.418

Review 2.  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

3.  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

4.  Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover.

Authors:  Jason T Manka; Paige N Vinson; Karen J Gregory; Ya Zhou; Richard Williams; Kiran Gogi; Emily Days; Satya Jadhav; Elizabeth J Herman; Hilde Lavreysen; Claire Mackie; José M Bartolomé; Gregor J Macdonald; Thomas Steckler; J Scott Daniels; C David Weaver; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Shaun R Stauffer
Journal:  Bioorg Med Chem Lett       Date:  2012-08-24       Impact factor: 2.823

5.  Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships.

Authors:  Karen J Gregory; Meredith J Noetzel; Jerri M Rook; Paige N Vinson; Shaun R Stauffer; Alice L Rodriguez; Kyle A Emmitte; Ya Zhou; Aspen C Chun; Andrew S Felts; Brian A Chauder; Craig W Lindsley; Colleen M Niswender; P Jeffrey Conn
Journal:  Mol Pharmacol       Date:  2012-08-03       Impact factor: 4.436

6.  Modification of Boc-Protected CAN508 via Acylation and Suzuki-Miyaura Coupling.

Authors:  Martin Pisár; Eva Schütznerová; Filip Hančík; Igor Popa; Zdeněk Trávníček; Petr Cankař
Journal:  Molecules       Date:  2018-01-12       Impact factor: 4.411
  6 in total

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