The first synthetic agonists of FFA2: Discovery and SAR of phenylacetamides as allosteric modulators

被引：75

作者：

Wang, Yingcai ^{[1
]}

Jiao, Xianyun ^{[1
]}

Kayser, Frank ^{[1
]}

Liu, Jiwen ^{[1
]}

Wang, Zhongyu ^{[1
]}

Wanska, Malgorzata ^{[1
]}

Greenberg, Joanne ^{[2
]}

Weiszmann, Jennifer ^{[2
]}

Ge, Hongfei ^{[2
]}

Tian, Hui ^{[2
]}

Wong, Simon ^{[3
]}

Schwandner, Ralf ^{[4
]}

Lee, Taeweon ^{[2
]}

Li, Yang ^{[2
]}

机构：

[1] Amgen Inc, Dept Chem, San Francisco, CA 94080 USA

[2] Amgen Inc, Dept Metab Disorders, San Francisco, CA 94080 USA

[3] Amgen Inc, Dept Pharmacokinet & Drug Metab, San Francisco, CA 94080 USA

[4] Amgen Res GmbH, Regensburg, Germany

来源：

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

关键词：

FFA2; GPR43; Allosteric; Agonist; Phenylacetamide; PROTEIN-COUPLED RECEPTORS; CHAIN FATTY-ACIDS; FUNCTIONAL-CHARACTERIZATION; NICOTINIC-ACID; IDENTIFICATION; DRUG; PROPIONATE; ACTIVATION;

D O I：

10.1016/j.bmcl.2009.11.112

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Free fatty acid receptor 2 (FFA2) is a G-protein coupled receptor for which only short-chain fatty acids (SCFAs) have been reported as endogenous ligands. We describe the discovery and optimization of phenylacetamides as allosteric agonists of FFA2. These novel ligands can suppress adipocyte lipolysis in vitro and reduce plasma FFA levels in vivo, suggesting that these allosteric modulators can serve as pharmacological tools for exploring the potential function of FFA2 in various disease conditions. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：493 / 498

页数：6

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