期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 24, 期 9, 页码 1981-1987出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2016.03.014
关键词
FFA1 agonist; GPR40; Ligand efficiency; Type 2 diabetes; Pyrrole
资金
- National Natural Science Foundation of China [81172932, 81273376]
- Natural Science Foundation of Jiangsu Province [BK2012356]
- Fundamental Research Funds for the Central Universities, China Pharmaceutical University [JKZD2013001]
The free fatty acid receptor 1 (FFA1) has gained significant interest as a novel antidiabetic target. Most of FFA1 agonists reported in the literature bearing a common biphenyl scaffold, which was crucial for toxicity verified by the researchers of Daiichi Sankyo. Herein, we describe the systematic exploration of non-biphenyl scaffold and further chemical modification of the optimal pyrrole scaffold. All of these efforts led to the identification of compound 11 as a potent and orally bioavailable FFA1 agonist without the risk of hypoglycemia. Further molecular modeling studies promoted the understanding of ligand-binding pocket and might help to design more promising FFA1 agonists. (C) 2016 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据