Literature DB >> 21067920

4-aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators.

Hui Xiong1, Todd A Brugel, Michael Balestra, Dean G Brown, Kelly A Brush, Caprice Hightower, Lindsay Hinkley, Valerie Hoesch, James Kang, Gerard M Koether, John P McCauley, Francis M McLaren, Laura M Panko, Thomas R Simpson, Reed W Smith, James M Woods, Becky Brockel, Vijay Chhajlani, Reto A Gadient, Nathan Spear, Linda A Sygowski, Minli Zhang, Jalaj Arora, Nathalie Breysse, Julie M Wilson, Methvin Isaac, Abdelmalik Slassi, Megan M King.   

Abstract

Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent activity and desired drug-like properties. Compound 2b was further characterized as a PAM using several in vitro experiments, and produced robust activity in several preclinical animal models.
Copyright © 2010 Elsevier Ltd. All rights reserved.

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Year:  2010        PMID： 21067920     DOI： 10.1016/j.bmcl.2010.10.036

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


  10 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

2.  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

3.  Discovery and Preclinical Evaluation of BMS-955829, a Potent Positive Allosteric Modulator of mGluR5.

Authors:  Fukang Yang; Lawrence B Snyder; Anand Balakrishnan; Jeffrey M Brown; Digavalli V Sivarao; Amy Easton; Alda Fernandes; Michael Gulianello; Umesh M Hanumegowda; Hong Huang; Yanling Huang; Kelli M Jones; Yu-Wen Li; Michele Matchett; Gail Mattson; Regina Miller; Kenneth S Santone; Arun Senapati; Eric E Shields; Frank J Simutis; Ryan Westphal; Valerie J Whiterock; Joanne J Bronson; John E Macor; Andrew P Degnan
Journal:  ACS Med Chem Lett       Date:  2016-01-04       Impact factor: 4.345

4.  Discovery and SAR of a novel series of non-MPEP site mGlu₅ PAMs based on an aryl glycine sulfonamide scaffold.

Authors:  Alice L Rodriguez; Ya Zhou; Richard Williams; C David Weaver; Paige N Vinson; Eric S Dawson; Thomas Steckler; Hilde Lavreysen; Claire Mackie; José M Bartolomé; Gregor J Macdonald; J Scott Daniels; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Shaun R Stauffer
Journal:  Bioorg Med Chem Lett       Date:  2012-10-23       Impact factor: 2.823

Review 5.  Metabotropic glutamate receptors as therapeutic targets for schizophrenia.

Authors:  Paige N Vinson; P Jeffrey Conn
Journal:  Neuropharmacology       Date:  2011-05-19       Impact factor: 5.250

6.  Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold.

Authors:  Richard Williams; Jason T Manka; Alice L Rodriguez; Paige N Vinson; Colleen M Niswender; C David Weaver; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Shaun R Stauffer
Journal:  Bioorg Med Chem Lett       Date:  2011-01-18       Impact factor: 2.823

Review 7.  Emerging approaches for treatment of schizophrenia: modulation of glutamatergic signaling.

Authors:  Meredith J Noetzel; Carrie K Jones; P Jeffrey Conn
Journal:  Discov Med       Date:  2012-11       Impact factor: 2.970

8.  N-aryl piperazine metabotropic glutamate receptor 5 positive allosteric modulators possess efficacy in preclinical models of NMDA hypofunction and cognitive enhancement.

Authors:  K J Gregory; E J Herman; A J Ramsey; A S Hammond; N E Byun; S R Stauffer; J T Manka; S Jadhav; T M Bridges; C D Weaver; C M Niswender; T Steckler; W H Drinkenburg; A Ahnaou; H Lavreysen; G J Macdonald; J M Bartolomé; C Mackie; B J Hrupka; M G Caron; T L Daigle; C W Lindsley; P J Conn; C K Jones
Journal:  J Pharmacol Exp Ther       Date:  2013-08-21       Impact factor: 4.030

9.  Tetrahydronaphthyridine and dihydronaphthyridinone ethers as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu₅).

Authors:  Mark Turlington; Chrysa Malosh; Jon Jacobs; Jason T Manka; Meredith J Noetzel; Paige N Vinson; Satyawan Jadhav; Elizabeth J Herman; Hilde Lavreysen; Claire Mackie; José M Bartolomé-Nebreda; Susana Conde-Ceide; M Luz Martín-Martín; Han Min Tong; Silvia López; 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:  J Med Chem       Date:  2014-06-25       Impact factor: 7.446

10.  Simplified Procedure for General Synthesis of Monosubstituted Piperazines-From a Batch Reaction Vessel to a Flow (Microwave) Reactor.

Authors:  Dana Němečková; Eva Havránková; Jan Šimbera; Richard Ševčík; Pavel Pazdera
Journal:  Molecules       Date:  2020-05-06       Impact factor: 4.411
  10 in total

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