3-芳基-3-乙氧基丙酸作为口服活性GPR40激动剂的发现。
Discovery of 3-aryl-3-ethoxypropanoic acids as orally active GPR40 agonists.
作者信息
Takano Rieko, Yoshida Masao, Inoue Masahiro, Honda Takeshi, Nakashima Ryutaro, Matsumoto Koji, Yano Tatsuya, Ogata Tsuneaki, Watanabe Nobuaki, Toda Narihiro
机构信息
R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
出版信息
Bioorg Med Chem Lett. 2014 Jul 1;24(13):2949-53. doi: 10.1016/j.bmcl.2014.04.065. Epub 2014 Apr 26.
The 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.
G蛋白偶联受体40（GPR40）介导胰腺β细胞中葡萄糖刺激的胰岛素分泌增强。GPR40激动剂作为一种新型的具有葡萄糖依赖性的胰岛素促分泌剂，用于治疗2型糖尿病，一直备受关注。对化合物1的优化研究产生了一种强效且具有生物利用度的GPR40激动剂24，其在大鼠口服葡萄糖耐量试验中显示出胰岛素分泌和降血糖作用。化合物24是一种新型胰岛素促分泌剂的潜在先导化合物，具有低血糖风险低的特点。
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