Efficacy switching SAR of mGluR5 allosteric modulators: Highly potent positive and negative modulators from one chemotype

被引：24

作者：

Sams, Anette Graven ^{[1
,2
]}

Mikkelsen, Gitte Kobberoe ^{[1
,2
]}

Brodbeck, Robbin M. ^{[3
]}

Pu, Xiaosui ^{[3
]}

Ritzen, Andreas ^{[1
,2
]}

机构：

[1] H Lundbeck & Co AS, Discovery Chem, DK-2500 Valby, Denmark

[2] H Lundbeck & Co AS, DMPK, DK-2500 Valby, Denmark

[3] Lundbeck Res USA Inc, ST Glutamate Biol 1, Paramus, NJ 07652 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 11期

关键词：

Glutamate; mGluR5; Allosteric modulator; PAM; NAM; Efficacy switching; METABOTROPIC GLUTAMATE RECEPTORS; RAT BEHAVIORAL-MODELS; METHYL-D-ASPARTATE; IN-VIVO ACTIVITY; ANTIPSYCHOTIC-LIKE; ANTAGONIST; DISCOVERY; MPEP; GLUTAMATE-RECEPTOR-5; PHARMACOLOGY;

D O I：

10.1016/j.bmcl.2011.03.103

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of metabotropic glutamate 5 receptor (mGluR5) allosteric ligands with positive, negative or no modulatory efficacy is described. The ability of this series to yield both mGluR5 PAMs and NAMs with single-digit nanomolar potency is unusual, and the underlying SAR is detailed. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3407 / 3410

页数：4

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