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Bioorg. Med. Chem. Lett. · Jul 2014
Discovery of 3-aryl-3-ethoxypropanoic acids as orally active GPR40 agonists.
- Rieko Takano, Masao Yoshida, Masahiro Inoue, Takeshi Honda, Ryutaro Nakashima, Koji Matsumoto, Tatsuya Yano, Tsuneaki Ogata, Nobuaki Watanabe, and Narihiro Toda.
- R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
- Bioorg. Med. Chem. Lett. 2014 Jul 1; 24 (13): 2949-53.
AbstractThe G protein-coupled receptor 40 (GPR40) mediates enhancement of glucose-stimulated insulin secretion in pancreatic β cells. The GPR40 agonist has been attracting attention as a novel insulin secretagogue with glucose dependency for the treatment of type 2 diabetes. The optimization study of compound 1 led to a potent and bioavailable GPR40 agonist 24, which showed insulin secretion and glucose lowering effects in rat OGTT. Compound 24 is a potential lead compound for a novel insulin secretagogue with a low risk of hypoglycemia. Copyright © 2014 Elsevier Ltd. All rights reserved.
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