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

被引：114

作者：

Roppe, J ^{[1
]}

Smith, ND ^{[1
]}

Huang, DH ^{[1
]}

Tehrani, L ^{[1
]}

Wang, BW ^{[1
]}

Anderson, J ^{[1
]}

Brodkin, J ^{[1
]}

Chung, J ^{[1
]}

Jiang, XH ^{[1
]}

King, C ^{[1
]}

Munoz, B ^{[1
]}

Varney, MA ^{[1
]}

Prasit, P ^{[1
]}

Cosford, NDP ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 19期

关键词：

D O I：

10.1021/jm049828c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 ED50 = 5.4 mg/kg (po) when dosed acutely. In this model the anxiolytic effects of 47 rapidly tolerate on repeated dosing.

引用

页码：4645 / 4648

页数：4

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