Literature DB >> 15225713

5-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-2,3'-bipyridine: a highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist with anxiolytic activity.

Jeffrey R Roppe1, Bowei Wang, Dehua Huang, Lida Tehrani, Theodore Kamenecka, Edwin J Schweiger, Jeffery J Anderson, Jesse Brodkin, Xiaohui Jiang, Merryl Cramer, Janice Chung, Grace Reyes-Manalo, Benito Munoz, Nicholas D P Cosford.   

Abstract

Structure-activity relationship studies leading to the discovery of a new, orally active mGlu5 receptor antagonist are described. The title compound, 5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-2,3'-bipyridine, is highly potent in vitro, has good in vivo receptor occupancy, and is efficacious in the rat fear-potentiated startle model of anxiety following oral dosing.

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Year:  2004        PMID： 15225713     DOI： 10.1016/j.bmcl.2004.05.037

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


  13 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.  Partial mGlu₅ Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects.

Authors:  Robert W Gould; Russell J Amato; Michael Bubser; Max E Joffe; Michael T Nedelcovych; Analisa D Thompson; Hilary H Nickols; Johannes P Yuh; Xiaoyan Zhan; Andrew S Felts; Alice L Rodriguez; Ryan D Morrison; Frank W Byers; Jerri M Rook; John S Daniels; Colleen M Niswender; P Jeffrey Conn; Kyle A Emmitte; Craig W Lindsley; Carrie K Jones
Journal:  Neuropsychopharmacology       Date:  2015-08-28       Impact factor: 7.853

3.  Structure-activity relationships comparing N-(6-methylpyridin-yl)-substituted aryl amides to 2-methyl-6-(substituted-arylethynyl)pyridines or 2-methyl-4-(substituted-arylethynyl)thiazoles as novel metabotropic glutamate receptor subtype 5 antagonists.

Authors:  Santosh S Kulkarni; Mu-Fa Zou; Jianjing Cao; Jeffrey R Deschamps; Alice L Rodriguez; P Jeffrey Conn; Amy Hauck Newman
Journal:  J Med Chem       Date:  2009-06-11       Impact factor: 7.446

4.  Synthesis and SAR of a mGluR5 allosteric partial antagonist lead: unexpected modulation of pharmacology with slight structural modifications to a 5-(phenylethynyl)pyrimidine scaffold.

Authors:  Sameer Sharma; Alice L Rodriguez; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2008-05-29       Impact factor: 2.823

Review 5.  Allosteric modulators of g protein-coupled receptors: future therapeutics for complex physiological disorders.

Authors:  Liyun Wang; Bronwen Martin; Randall Brenneman; Louis M Luttrell; Stuart Maudsley
Journal:  J Pharmacol Exp Ther       Date:  2009-08-10       Impact factor: 4.030

6.  Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS.

Authors:  Ya Zhou; Alice L Rodriguez; Richard Williams; C David Weaver; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2009-10-28       Impact factor: 2.823

7.  Social Isolation During Adolescence Induces Anxiety Behaviors and Enhances Firing Activity in BLA Pyramidal Neurons via mGluR5 Upregulation.

Authors:  Song Lin; Xin Li; Yi-Hua Chen; Feng Gao; Hao Chen; Neng-Yuan Hu; Lang Huang; Zheng-Yi Luo; Ji-Hong Liu; Qiang-Long You; Ya-Nan Yin; Ze-Lin Li; Xiao-Wen Li; Zhuo-Jun Du; Jian-Ming Yang; Tian-Ming Gao
Journal:  Mol Neurobiol       Date:  2017-09-15       Impact factor: 5.590

8.  Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype.

Authors:  Alice L Rodriguez; Richard Williams; Ya Zhou; Stacey R Lindsley; Uyen Le; Mark D Grier; C David Weaver; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2009-05-03       Impact factor: 2.823

9.  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

10.  VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy.

Authors:  Hilary Highfield Nickols; Joannes P Yuh; Karen J Gregory; Ryan D Morrison; Brittney S Bates; Shaun R Stauffer; Kyle A Emmitte; Michael Bubser; Weimin Peng; Michael T Nedelcovych; Analisa Thompson; Xiaohui Lv; Zixiu Xiang; J Scott Daniels; Colleen M Niswender; Craig W Lindsley; Carrie K Jones; P Jeffrey Conn
Journal:  J Pharmacol Exp Ther       Date:  2015-10-26       Impact factor: 4.030
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