Literature DB >> 15341479

Discovery of novel heteroarylazoles that are metabotropic glutamate subtype 5 receptor antagonists with anxiolytic activity.

Jeffrey Roppe, Nicholas D Smith, Dehua Huang, Lida Tehrani, Bowei Wang, Jeffrey Anderson, Jesse Brodkin, Janice Chung, Xiaohui Jiang, Christopher King, Benito Munoz, Mark A Varney, Petpiboon Prasit, Nicholas D P Cosford.   

Abstract

The highly potent, selective, and brain-penetrant metabotropic glutamate subtype 5 (mGlu5) receptor antagonists 3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile (47) and 3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile (48) are reported. Compound 47 is active in the rat fear-potentiated startle (FPS) model of anxiety with ED(50) = 5.4 mg/kg (po) when dosed acutely. In this model the anxiolytic effects of 47 rapidly tolerate on repeated dosing.

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Year:  2004        PMID： 15341479     DOI： 10.1021/jm049828c

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


  15 in total

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

Authors:  Santosh S Kulkarni; Amy Hauck Newman
Journal:  Bioorg Med Chem Lett       Date:  2007-01-04       Impact factor: 2.823

2.  Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists.

Authors:  Santosh S Kulkarni; Amy Hauck Newman
Journal:  Bioorg Med Chem Lett       Date:  2007-03-24       Impact factor: 2.823

3.  Synthesis of 2-(1,2,4-oxadiazol-3-yl)quinazolin-4(3H)-ones from diaminoglyoxime-based nitrones.

Authors:  Rahim Hosseinzadeh-Khanmiri; Abolghasem Moghimi; Ahmad Shaabani; Hassan Valizadeh; Seik Weng Ng
Journal:  Mol Divers       Date:  2015-04-22       Impact factor: 2.943

4.  Bis-aryloxadiazoles as effective activators of the aryl hydrocarbon receptor.

Authors:  Kaitlin J Basham; Vasudev R Bhonde; Collin Kieffer; James B C Mack; Matthew Hess; Bryan E Welm; Ryan E Looper
Journal:  Bioorg Med Chem Lett       Date:  2014-04-13       Impact factor: 2.823

5.  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

6.  Stepwise aromatic nucleophilic substitution in continuous flow. Synthesis of an unsymmetrically substituted 3,5-diamino-benzonitrile library.

Authors:  László Lengyel; Viktor Gyóllai; Tamás Nagy; György Dormán; Péter Terleczky; Viktor Háda; Katalin Nógrádi; Ferenc Sebok; László Urge; Ferenc Darvas
Journal:  Mol Divers       Date:  2010-12-29       Impact factor: 2.943

7.  Investigation on tolerance development to subchronic blockade of mGluR5 in models of learning, anxiety, and levodopa-induced dyskinesia in rats.

Authors:  Andreas Gravius; Andrzej Dekundy; Jens Nagel; Lorenzo Morè; Małgorzata Pietraszek; Wojciech Danysz
Journal:  J Neural Transm (Vienna)       Date:  2008-08-09       Impact factor: 3.575

8.  Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors.

Authors:  Zhuang Jin; Pasha Khan; Youseung Shin; Jingyi Wang; Li Lin; Michael D Cameron; Jon M Lindstrom; Paul J Kenny; Theodore M Kamenecka
Journal:  Bioorg Med Chem Lett       Date:  2013-11-28       Impact factor: 2.823

9.  Rapid multistep synthesis of 1,2,4-oxadiazoles in a single continuous microreactor sequence.

Authors:  Daniel Grant; Russell Dahl; Nicholas D P Cosford
Journal:  J Org Chem       Date:  2008-08-08       Impact factor: 4.354

10.  Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships.

Authors:  Karen J Gregory; Meredith J Noetzel; Jerri M Rook; Paige N Vinson; Shaun R Stauffer; Alice L Rodriguez; Kyle A Emmitte; Ya Zhou; Aspen C Chun; Andrew S Felts; Brian A Chauder; Craig W Lindsley; Colleen M Niswender; P Jeffrey Conn
Journal:  Mol Pharmacol       Date:  2012-08-03       Impact factor: 4.436
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