The identification of structurally novel, selective, orally bioavailable positive modulators of mGluR2

被引：17

作者：

D'Alessandro, Pier L. ^{[1
]}

Corti, Corrado ^{[2
]}

Roth, Adelheid ^{[2
]}

Ugolini, Annarosa ^{[2
]}

Sava, Anna ^{[2
]}

Montanari, Dino ^{[2
]}

Bianchi, Federica ^{[2
]}

Garland, Stephen L. ^{[3
]}

Powney, Ben ^{[3
]}

Koppe, Emma L. ^{[3
]}

Rocheville, Magalie ^{[3
]}

Osborne, Greg ^{[3
]}

Perez, Paloma ^{[4
]}

de la Fuente, Jesus ^{[4
]}

De Los Frailes, Maite ^{[4
]}

Smith, Paul W. ^{[1
]}

Branch, Clive ^{[1
]}

Nash, David ^{[1
]}

Watson, Stephen P. ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, Neurosci Ctr Excellence Drug Discovery, Harlow, Essex, England

[2] GlaxoSmithKline Inc, Neurosci Ctr Excellence Drug Discovery, Med Res Ctr, Verona, Italy

[3] GlaxoSmithKline Inc, Mol Discovery Res, Harlow, Essex, England

[4] GlaxoSmithKline Inc, Mol Discovery Res, Madrid, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 02期

关键词：

Metabotropic glutamate receptor ligand; Metabotropic glutamate receptor; Positive allosteric modulator; mGluR; mGlu; mGluR2; METABOTROPIC GLUTAMATE RECEPTORS; PHARMACOLOGICAL CHARACTERIZATION; LY354740; AGONIST; POTENT; 2-(4-PYRIDIN-2-YLPIPERAZIN-1-YLMETHYL)-1H-BENZIMIDAZOLE; ACTIVATION; EFFICACY;

D O I：

10.1016/j.bmcl.2009.11.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The optimisation of an HTS hit series (1) leading to the identification of structurally novel, selective, orally bioavailable mGluR2 positive modulators GSK1331258 and GSK1331268 is described. Structure-activity relationships, attenuation of dopaminergic activity, and potentiation of mGluR2 responses in rat hippocampal MPP-DG synapses are also reported. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：759 / 762

页数：4

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