Literature DB >> 20667732

Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS).

Darren W Engers1, Patrick R Gentry, Richard Williams, Julie D Bolinger, C David Weaver, Usha N Menon, P Jeffrey Conn, Craig W Lindsley, Colleen M Niswender, Corey R Hopkins.   

Abstract

Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu(4) positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu(4) PAM reported to date. Copyright 2010 Elsevier Ltd. All rights reserved.

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Year:  2010        PMID： 20667732      PMCID： PMC2922490          DOI： 10.1016/j.bmcl.2010.07.007

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


  15 in total

1.  Development of a custom high-throughput preparative liquid chromatography/mass spectrometer platform for the preparative purification and analytical analysis of compound libraries.

Authors:  William Leister; Kimberly Strauss; David Wisnoski; Zhijian Zhao; Craig Lindsley
Journal:  J Comb Chem       Date:  2003 May-Jun

2.  Role of GRM4 in idiopathic generalized epilepsies analysed by genetic association and sequence analysis.

Authors:  Hiltrud Muhle; Sarah von Spiczak; Verena Gaus; Serife Kara; Ingo Helbig; Jochen Hampe; Andre Franke; Yvonne Weber; Holger Lerche; Ailing A Kleefuss-Lie; Christian E Elger; Stefan Schreiber; Ulrich Stephani; Thomas Sander
Journal:  Epilepsy Res       Date:  2010-03-24       Impact factor: 3.045

Review 3.  Recent progress in the development of mGluR4 positive allosteric modulators for the treatment of Parkinson's disease.

Authors:  Craig W Lindsley; Colleen M Niswender; Darren W Engers; Corey R Hopkins
Journal:  Curr Top Med Chem       Date:  2009       Impact factor: 3.295

4.  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

5.  Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4.

Authors:  Colleen M Niswender; Kari A Johnson; C David Weaver; Carrie K Jones; Zixiu Xiang; Qingwei Luo; Alice L Rodriguez; Joy E Marlo; Tomas de Paulis; Analisa D Thompson; Emily L Days; Tasha Nalywajko; Cheryl A Austin; Michael Baxter Williams; Jennifer E Ayala; Richard Williams; Craig W Lindsley; P Jeffrey Conn
Journal:  Mol Pharmacol       Date:  2008-07-29       Impact factor: 4.436

Review 6.  Metabotropic glutamate receptors: physiology, pharmacology, and disease.

Authors:  Colleen M Niswender; P Jeffrey Conn
Journal:  Annu Rev Pharmacol Toxicol       Date:  2010       Impact factor: 13.820

7.  Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead.

Authors:  Richard Williams; Colleen M Niswender; Qingwei Luo; Uyen Le; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2008-12-25       Impact factor: 2.823

8.  (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection.

Authors:  M Maj; V Bruno; Z Dragic; R Yamamoto; G Battaglia; W Inderbitzin; N Stoehr; T Stein; F Gasparini; I Vranesic; R Kuhn; F Nicoletti; P J Flor
Journal:  Neuropharmacology       Date:  2003-12       Impact factor: 5.250

9.  Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel mGluR4 positive allosteric modulators.

Authors:  Colleen M Niswender; Evan P Lebois; Qingwei Luo; Kwangho Kim; Hubert Muchalski; Huiyong Yin; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2008-08-29       Impact factor: 2.823

10.  Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4).

Authors:  Richard Williams; Kari A Johnson; Patrick R Gentry; Colleen M Niswender; Charles D Weaver; P Jeffrey Conn; Craig W Lindsley; Corey R Hopkins
Journal:  Bioorg Med Chem Lett       Date:  2009-07-18       Impact factor: 2.823
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  13 in total

1.  Allosteric modulation of the group III mGlu4 receptor provides functional neuroprotection in the 6-hydroxydopamine rat model of Parkinson's disease.

Authors:  Matthew J Betts; Michael J O'Neill; Susan Duty
Journal:  Br J Pharmacol       Date:  2012-08       Impact factor: 8.739

2.  Discovery, synthesis, and structure-activity relationship development of a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): characterization of a novel positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu(4)) with oral efficacy in an antiparkinsonian animal model.

Authors:  Carrie K Jones; Darren W Engers; Analisa D Thompson; Julie R Field; Anna L Blobaum; Stacey R Lindsley; Ya Zhou; Rocco D Gogliotti; Satyawan Jadhav; Rocio Zamorano; Jim Bogenpohl; Yoland Smith; Ryan Morrison; J Scott Daniels; C David Weaver; P Jeffrey Conn; Craig W Lindsley; Colleen M Niswender; Corey R Hopkins
Journal:  J Med Chem       Date:  2011-10-19       Impact factor: 7.446

3.  Iterative experimental and virtual high-throughput screening identifies metabotropic glutamate receptor subtype 4 positive allosteric modulators.

Authors:  Ralf Mueller; Eric S Dawson; Colleen M Niswender; Mariusz Butkiewicz; Corey R Hopkins; C David Weaver; Craig W Lindsley; P Jeffrey Conn; Jens Meiler
Journal:  J Mol Model       Date:  2012-05-17       Impact factor: 1.810

4.  Functional selectivity induced by mGlu₄ receptor positive allosteric modulation and concomitant activation of Gq coupled receptors.

Authors:  Shen Yin; Rocio Zamorano; P Jeffrey Conn; Colleen M Niswender
Journal:  Neuropharmacology       Date:  2012-03-09       Impact factor: 5.250

Review 5.  Recent progress on the identification of metabotropic glutamate 4 receptor ligands and their potential utility as CNS therapeutics.

Authors:  Albert J Robichaud; Darren W Engers; Craig W Lindsley; Corey R Hopkins
Journal:  ACS Chem Neurosci       Date:  2011-06-14       Impact factor: 4.418

6.  Discovery and characterization of a novel series of N-phenylsulfonyl-1H-pyrrole picolinamides as positive allosteric modulators of the metabotropic glutamate receptor 4 (mGlu4).

Authors:  Rocco D Gogliotti; Anna L Blobaum; Ryan M Morrison; J Scott Daniels; James M Salovich; Yiu-Yin Cheung; Alice L Rodriguez; Matthew T Loch; P Jeffrey Conn; Craig W Lindsley; Colleen M Niswender; Corey R Hopkins
Journal:  Bioorg Med Chem Lett       Date:  2016-05-11       Impact factor: 2.823

7.  Metabotropic glutamate receptor 4 in the basal ganglia of parkinsonian monkeys: ultrastructural localization and electrophysiological effects of activation in the striatopallidal complex.

Authors:  James Bogenpohl; Adriana Galvan; Xing Hu; Thomas Wichmann; Yoland Smith
Journal:  Neuropharmacology       Date:  2012-05-23       Impact factor: 5.250

8.  Solution-phase parallel synthesis and SAR of homopiperazinyl analogs as positive allosteric modulators of mGlu₄.

Authors:  Yiu-Yin Cheung; Rocio Zamorano; Anna L Blobaum; C David Weaver; P Jeffrey Conn; Craig W Lindsley; Colleen M Niswender; Corey R Hopkins
Journal:  ACS Comb Sci       Date:  2011-02-21       Impact factor: 3.784

9.  Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats.

Authors:  Darren W Engers; Julie R Field; Uyen Le; Ya Zhou; Julie D Bolinger; Rocio Zamorano; Anna L Blobaum; Carrie K Jones; Satyawan Jadhav; C David Weaver; P Jeffrey Conn; Craig W Lindsley; Colleen M Niswender; Corey R Hopkins
Journal:  J Med Chem       Date:  2011-01-19       Impact factor: 7.446

10.  Discovery of 3-aminopicolinamides as metabotropic glutamate receptor subtype 4 (mGlu4) positive allosteric modulator warheads engendering CNS exposure and in vivo efficacy.

Authors:  Rocco D Gogliotti; Darren W Engers; Pedro M Garcia-Barrantes; Joseph D Panarese; Patrick R Gentry; Anna L Blobaum; Ryan D Morrison; J Scott Daniels; Analisa D Thompson; Carrie K Jones; P Jeffrey Conn; Colleen M Niswender; Craig W Lindsley; Corey R Hopkins
Journal:  Bioorg Med Chem Lett       Date:  2016-04-19       Impact factor: 2.823
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