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

被引：379

作者：

Cosford, NDP ^{[1
]}

Tehrani, L ^{[1
]}

Roppe, J ^{[1
]}

Schweiger, E ^{[1
]}

Smith, ND ^{[1
]}

Anderson, J ^{[1
]}

Bristow, L ^{[1
]}

Brodkin, J ^{[1
]}

Jiang, XH ^{[1
]}

McDonald, I ^{[1
]}

Rao, S ^{[1
]}

Washburn, M ^{[1
]}

Varney, MA ^{[1
]}

机构：

[1] Merck Res Labs, San Diego, CA 92121 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 02期

关键词：

D O I：

10.1021/jm025570j

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：204 / 206

页数：3

共 21 条

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