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Literature DB >> 12519057

3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity.

Nicholas D P Cosford¹, Lida Tehrani, Jeffrey Roppe, Edwin Schweiger, Nicholas D Smith, Jeffrey Anderson, Linda Bristow, Jesse Brodkin, Xiaohui Jiang, Ian McDonald, Sara Rao, Mark Washburn, Mark A Varney.

Abstract

2-Methyl-6-(phenylethynyl)pyridine (3), a potent noncompetitive mGlu5 receptor antagonist widely used to characterize the pharmacology of mGlu5 receptors, suffers from a number of shortcomings as a therapeutic agent, including off-target activity and poor aqueous solubility. Seeking to improve the properties of 3 led to the synthesis of compound 9, a highly selective mGlu5 receptor antagonist that is 5-fold more potent than 3 in the rat fear-potentiated startle model of anxiety.

Entities: Chemical Disease Species

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Year: 2003 PMID： 12519057 DOI： 10.1021/jm025570j

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

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Cited

103 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. Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery.

Authors: Bruce J Melancon; Corey R Hopkins; Michael R Wood; Kyle A Emmitte; Colleen M Niswender; Arthur Christopoulos; P Jeffrey Conn; Craig W Lindsley
Journal: J Med Chem Date: 2012-01-06 Impact factor: 7.446

3. In vivo positron emission tomography imaging with [¹¹C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons.

Authors: Christine DeLorenzo; Matthew S Milak; Kathleen G Brennan; J S Dileep Kumar; J John Mann; Ramin V Parsey
Journal: Eur J Nucl Med Mol Imaging Date: 2011-01-29 Impact factor: 9.236

4. Interaction of blockers of ionotropic NMDA receptors and metabotropic glutamate receptors in a working memory test in rats.

Authors: Y A Novitskaya; O A Dravolina; E E Zvartau; W Danysz; A Y Bespalov
Journal: Neurosci Behav Physiol Date: 2010-07-17

5. 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-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity.

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.

2. Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery.

3. In vivo positron emission tomography imaging with [¹¹C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons.

4. Interaction of blockers of ionotropic NMDA receptors and metabotropic glutamate receptors in a working memory test in rats.

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

Review 6. Ionotropic and metabotropic glutamate receptor structure and pharmacology.

7. Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors.

8. Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists.

9. Efficient and regioselective halogenations of 2-amino-1,3-thiazoles with copper salts.

Review 10. Targeting glutamatergic signaling for the development of novel therapeutics for mood disorders.