Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor:: Synthesis and subtype selectivity of N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethyl-amine

被引：168

作者：

Johnson, MP ^{[1
]}

Baez, M ^{[1
]}

Jagdmann, GE ^{[1
]}

Britton, TC ^{[1
]}

Large, TH ^{[1
]}

Callagaro, DO ^{[1
]}

Tizzano, JP ^{[1
]}

Monn, JA ^{[1
]}

Schoepp, DD ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 15期

关键词：

D O I：

10.1021/jm034015u

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This report describes recently discovered novel allosteric modulators of metabotropic glutamate2 (mGlu2) receptors. These pyridylmethylsulfonamides (e.g., 3) potentiate glutamate, shifting agonist potency by 2-fold. This effect was specific for mGlu2 (vs mGlu1,3-8 receptors). Also, 3 failed to potentiate a chimeric mGlu2/1 receptor, demonstrating the mGlu2 transmembrane region's critical involvement. In a fear-potentiated startle model, 3 showed anxiolytic activity that was prevented by mGlu2/3 antagonist pretreatment. Thus, these pyridylmethylsulfonamides represent the first mGlu2 receptor potentiators discovered.

引用

页码：3189 / 3192

页数：4

共 25 条

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