Exploration of phenylpropanoic acids as agonists of the free fatty acid receptor 4 (FFA4): Identification of an orally efficacious FFA4 agonist

被引：18
|
作者：
Sparks, Steven M. [1 ]
Aquino, Christopher
Banker, Pierette
Collins, Jon L.
Cowan, David
Diaz, Caroline
Dock, Steven T.
Hertzog, Donald L.
Liang, Xi
Swiger, Erin D.
Yuen, Josephine
Chen, Grace
Jayawickreme, Channa
Moncol, David
Nystrom, Christopher
Rash, Vincent
Rimele, Thomas
Roller, Shane
Ross, Sean
机构：
[1] Viamet Pharmaceut, 4505 Emperor Blvd,Suite 300, Durham, NC 27703 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 05期
关键词：
Free fatty acid receptor 4; GPR120; Free fatty acid receptor 1; Phenylpropanoic acid; Type; 2; diabetes; PROTEIN-COUPLED RECEPTORS; INSULIN-SECRETION; THERAPEUTIC TARGET; GPR120; GPR40; INFLAMMATION; OMEGA-3-FATTY-ACIDS; PHARMACOLOGY; RESISTANCE; OBESITY;
D O I：
10.1016/j.bmcl.2017.01.034
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The long chain free fatty acid receptor 4 (FFA4/GPR120) has recently been recognized as lipid sensor playing important roles in nutrient sensing and inflammation and thus holds potential as a therapeutic target for type 2 diabetes and metabolic syndrome. To explore the effects of stimulating this receptor in animal models of metabolic disease, we initiated work to identify agonists with appropriate pharmacokinetic properties to support progression into in vivo studies. Extensive SAR studies of a series of phenylpropanoic acids led to the identification of compound 29, a FFA4 agonist which lowers plasma glucose in two preclinical models of type 2 diabetes. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1278 / 1283
页数：6
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