Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor

被引：65

作者：

McKeown, Stephen C.

Corbett, David F.

Goetz, Aaron S.

Littleton, Thomas R.

Bigham, Eric

Briscoe, Celia P.

Peat, Andrew J.

Watson, Steve P.

Hickey, Deirdre M. B.

机构：

[1] GlaxoSmithKline, Mol Discovery Res, Harlow CM19 5AW, Essex, England

[2] GlaxoSmithKline, Res & Dev, Mol Discovery Res, Res Triangle Pk, NC 27709 USA

[3] GlaxoSmithKline, Metab Ctr Excellence Drug Discovery, Res & Dev, Res Triangle Pk, NC 27709 USA

[4] GlaxoSmithKline, Infect Dis Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 06期

关键词：

GPR40; agonist; diabetes; solid phase chemistry;

D O I：

10.1016/j.bmcl.2006.12.084

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery, synthesis and structure-activity relationship (SAR) of novel carboxylic acid agonists for GPR40 are described. Aryl propionic acid 1, identified from a high throughput screen, was selected for chemical exploration. Compound 2 was identified as our lead molecule through efficient solid phase combinatorial array chemistry and had an attractive in vitro and in vivo pharmacokinetic profile in rat. These ligands may prove useful in establishing a role for GPR40 in insulin regulation. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：1584 / 1589

页数：6

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