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

被引：41

作者：

Alagille, D

Baldwin, RM

Roth, BL

Wroblewski, JT

Grajkowska, E

Tamagnan, GD

机构：

[1] Yale Univ, Dept Psychiat, West Haven, CT 06516 USA

[2] VA Connecticut 116A2, West Haven, CT 06516 USA

[3] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA

[4] Case Western Reserve Univ, Sch Med, NIMH Psychoact Drug Screening, Cleveland, OH 44106 USA

[5] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA

[6] Inst Neurodegenerat Disorders, New Haven, CT 06510 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 01期

关键词：

mGluR5; synthesis; antagonist; metabotropic; gluatamate;

D O I：

10.1016/j.bmc.2004.09.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 IC50 = 13.5, 11.9, 21, 15nM, respectively). (C) 2004 Elsevier Ltd. All rights reserved.

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收藏

页码：197 / 209

页数：13

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