Discovery of Potent and Orally Bioavailable GPR40 Full Agonists Bearing Thiophen-2-ylpropanoic Acid Scaffold was written by Li, He;Huang, Qi;Chen, Cheng;Xu, Bin;Wang, He-Yao;Long, Ya-Qiu. And the article was included in Journal of Medicinal Chemistry in 2017.Reference of 1072951-54-2 This article mentions the following:
The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chem. and structurally diverse GPR40 agonists with high safety are pursued for the clin. development of GPR40-based pharmacotherapeutics. Herein we report our design and discovery of a new chemotype of GPR40 agonists free of the typical phenylpropanoic acid scaffold. The thiophen-2-ylpropanoic acid containing GPR40 modulators functioned as full agonists with high-efficacy response (Emax) and reduced lipophilicity. Significantly, the lead compound in this series, (R)-7k, exhibited more potent in vitro glucose-stimulated insulin secretion and in vivo glucose-lowering effects (10 mg/kg, po) than the GPR40 partial agonist TAK-875, which was once in phase III clin. trials, and high selectivity over the relevant receptors GPR120 and PPARγ. In the experiment, the researchers used many compounds, for example, (2,6-Dichloropyridin-4-yl)boronic acid (cas: 1072951-54-2Reference of 1072951-54-2).
(2,6-Dichloropyridin-4-yl)boronic acid (cas: 1072951-54-2) belongs to pyridine derivatives. Pyridine has a conjugated system of six π electrons that are delocalized over the ring. The molecule is planar and, thus, follows the Hückel criteria for aromatic systems. Pyridine groups exist in countless molecules, and their applications include catalysis, drug design, molecular recognition, and natural product synthesis.Reference of 1072951-54-2