Literature DB >> 21247167

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.

Darren W Engers1, 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.   

Abstract

Herein we report the discovery, synthesis, and evaluation of a series of N-(4-acetamido)-phenylpicolinamides as positive allosteric modulators of mGlu(4). Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats.

Entities:  

Mesh：

Substances：

Year:  2011        PMID： 21247167      PMCID： PMC3166797          DOI： 10.1021/jm101271s

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  17 in total

Review 1.  Allosteric modulators of group I metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives.

Authors:  Fabrizio Gasparini; Rainer Kuhn; Jean-Philippe Pin
Journal:  Curr Opin Pharmacol       Date:  2002-02       Impact factor: 5.547

2.  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

3.  An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction.

Authors:  Stephen P East; Samantha Bamford; Matthias G A Dietz; Christian Eickmeier; Adam Flegg; Boris Ferger; Mark J Gemkow; Ralf Heilker; Bastian Hengerer; Adrian Kotey; Pui Loke; Gerhard Schänzle; Hans-Dieter Schubert; John Scott; Mark Whittaker; Mildred Williams; Przemyslaw Zawadzki; Kai Gerlach
Journal:  Bioorg Med Chem Lett       Date:  2010-06-25       Impact factor: 2.823

Review 4.  Allosteric modulation of G protein-coupled receptors.

Authors:  Lauren T May; Katie Leach; Patrick M Sexton; Arthur Christopoulos
Journal:  Annu Rev Pharmacol Toxicol       Date:  2007       Impact factor: 13.820

5.  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

6.  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

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

Authors:  Darren W Engers; 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
Journal:  Bioorg Med Chem Lett       Date:  2010-07-08       Impact factor: 2.823

8.  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

9.  (-)-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

Review 10.  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
View more
  19 in total

1.  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

Review 2.  Parkinson's disease therapeutics: new developments and challenges since the introduction of levodopa.

Authors:  Yoland Smith; Thomas Wichmann; Stewart A Factor; Mahlon R DeLong
Journal:  Neuropsychopharmacology       Date:  2011-09-28       Impact factor: 7.853

3.  The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia.

Authors:  Ranjani Ponnazhagan; Ashley S Harms; Aaron D Thome; Asta Jurkuvenaite; Rocco Gogliotti; Colleen M Niswender; P Jeffrey Conn; David G Standaert
Journal:  J Neuroimmune Pharmacol       Date:  2016-02-12       Impact factor: 4.147

Review 4.  Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors.

Authors:  Craig W Lindsley; Kyle A Emmitte; Corey R Hopkins; Thomas M Bridges; Karen J Gregory; Colleen M Niswender; P Jeffrey Conn
Journal:  Chem Rev       Date:  2016-02-16       Impact factor: 60.622

5.  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

6.  The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease.

Authors:  Zixiu Xiang; Analisa D Thompson; John T Brogan; Michael L Schulte; Bruce J Melancon; Debbie Mi; L Michelle Lewis; Bende Zou; Liya Yang; Ryan Morrison; Tammy Santomango; Frank Byers; Katrina Brewer; Jonathan S Aldrich; Haibo Yu; Eric S Dawson; Min Li; Owen McManus; Carrie K Jones; J Scott Daniels; Corey R Hopkins; Ximin Simon Xie; P Jeffrey Conn; C David Weaver; Craig W Lindsley
Journal:  ACS Chem Neurosci       Date:  2011-12-21       Impact factor: 4.418

Review 7.  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

8.  An allosteric modulator to control endogenous G protein-coupled receptors with light.

Authors:  Silvia Pittolo; Xavier Gómez-Santacana; Kay Eckelt; Xavier Rovira; James Dalton; Cyril Goudet; Jean-Philippe Pin; Artur Llobet; Jesús Giraldo; Amadeu Llebaria; Pau Gorostiza
Journal:  Nat Chem Biol       Date:  2014-08-31       Impact factor: 15.040

9.  Development and Antiparkinsonian Activity of VU0418506, a Selective Positive Allosteric Modulator of Metabotropic Glutamate Receptor 4 Homomers without Activity at mGlu2/4 Heteromers.

Authors:  Colleen M Niswender; Carrie K Jones; Xin Lin; Michael Bubser; Analisa Thompson Gray; Anna L Blobaum; Darren W Engers; Alice L Rodriguez; Matthew T Loch; J Scott Daniels; Craig W Lindsley; Corey R Hopkins; Jonathan A Javitch; P Jeffrey Conn
Journal:  ACS Chem Neurosci       Date:  2016-08-05       Impact factor: 4.418

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
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.