Discovery of novel orally bioavailable GPR40 agonists
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- 作者：Hejun Lu ; lvhj@shhrp.com ; Hongbo Fei ; Fanglong Yang ; Suxin Zheng ; Qiyue Hu ; Lei Zhang ; Jijun Yuan ; Jun Feng ; Piaoyang Sun ; Qing Dong
- 关键词：Diabetes ; GPR40 ; Agonist ; Orally bioavailable ; Species specificity
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：15 May, 2013
- 年：2013
- 卷：23
- 期：10
- 页码：2920-2924
- 全文大小：882 K
文摘
The GPR40 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. A series of novel orally bioavailable GPR40 agonists was discovered. SAR study and structural optimization led to identification of compounds 28a and 30a as potent GPR40 agonists with superior physiochemical properties and robust in vivo efficacy in rhesus monkeys.