期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 22, 期 2, 页码 1267-1270出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.10.118
关键词
GPR40; FFA1; Anti-diabetic; GPCR; Agonist; Insulin; Secretagogue
The discovery that certain long chain fatty acids potentiate glucose stimulated insulin secretion through the previously orphan receptor GPR40 sparked interest in GPR40 agonists as potential antidiabetic agents. Optimization of a series of beta-substituted phenylpropanoic acids led to the identification of (S)-3-(44(4'-(trifluoromethyl)biphenyl-3-yl)methoxy)phenyl)hex-4-ynoic acid (AMG 837) as a potent GPR40 agonist with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents. (C) 2011 Elsevier Ltd. All rights reserved.
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