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Literature DB >> 15582465

Synthesis and receptor assay of aromatic-ethynyl-aromatic derivatives with potent mGluR5 antagonist activity.

David Alagille¹, Ronald M Baldwin, Bryan L Roth, Jarda T Wroblewski, Ewa Grajkowska, Gilles D Tamagnan.

Abstract

Noncompetitive antagonists of the human metabotropic glutamate receptor subtype 5 (mGluR5) have been implicated as potential therapeutics for the treatment of a variety of nervous system disorders, including pain, anxiety, and drug addiction. To discover novel noncompetitive antagonists to the mGluR5, we initiated an SAR study around the known lead compounds MPEP and M-MPEP. Our results pointed out the critical role of the para position of the two aromatic rings, which leads to inactive products and permitted the discovery of potent mGluR5 antagonists (e.g., 16, 25, 28, 34 IC(50) = 13.5, 11.9, 21, 15 nM, respectively).

Entities: Chemical Disease Gene Species

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Year: 2005 PMID： 15582465 DOI： 10.1016/j.bmc.2004.09.042

Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641

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Cited

8 in total

1. 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

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. Structure-activity relationships in a novel series of 7-substituted-aryl quinolines and 5-substituted-aryl benzothiazoles at the metabotropic glutamate receptor subtype 5.

Authors: Peng Zhang; Mu-Fa Zou; Alice L Rodriguez; P Jeffrey Conn; Amy Hauck Newman
Journal: Bioorg Med Chem Date: 2010-03-27 Impact factor: 3.641

Synthesis and receptor assay of aromatic-ethynyl-aromatic derivatives with potent mGluR5 antagonist activity.

1. 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.

2. Identification of specific ligand-receptor interactions that govern binding and cooperativity of diverse modulators to a common metabotropic glutamate receptor 5 allosteric site.

3. Structure-activity relationships in a novel series of 7-substituted-aryl quinolines and 5-substituted-aryl benzothiazoles at the metabotropic glutamate receptor subtype 5.

4. Synthesis of deuterated 1,2,3-triazoles.

5. Potent mGluR5 antagonists: pyridyl and thiazolyl-ethynyl-3,5-disubstituted-phenyl series.

6. Synthesis and Evaluation of Metabotropic Glutamate Receptor Subtype 5 Antagonists Based on Fenobam().

7. Synthesis and photophysical properties of linear gold(I) complexes based on a CCC carbene.

8. Improved Syntheses of the Mglu₅ Antagonists MMPEP and MTEP Using Sonogashira Cross-Coupling.