Discovery of novel free fatty acid receptor 1 agonists bearing triazole core via click chemistry.
Discovery of novel free fatty acid receptor 1 agonists bearing triazole core via click chemistry.
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DOI：
10.1016/j.bmc.2016.08.068
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发表时间：
2016-11
影响因子：
3.5
通讯作者：
Zheng Li;Jianyong Yang;Xuekun Wang;Huilan Li;Chunxiao Liu;Nasi Wang;Wen-long Huang;Hai Qian
中科院分区：
文献类型：
--
作者：
Zheng Li;Jianyong Yang;Xuekun Wang;Huilan Li;Chunxiao Liu;Nasi Wang;Wen-long Huang;Hai Qian
The free fatty acid receptor 1 (FFA1/GPR40) is a novel antidiabetic target based on particular mechanism in enhancing glucose-stimulated insulin secretion. Most of reported FFA1 agonists, however, have been suffered from relatively high lipophilicity and molecular weight. Aiming to develop potent agonists with improved physicochemical property, 25 compounds containing triazole scaffold and various carboxylic acid fragments were synthesized via the click chemistry. Among them, the optimal lead compound26with relatively low lipophicity (LogD7.4= 1.95) and molecular weight (Mw = 391.78) exhibited a considerable FFA1 agonistic activity (36.15%). In addition, compound26revealed a significant improvement in the glucose tolerance with a 21.4% and 14.2% reduction of glucose AUC0–2hin normal ICR mice and type 2 diabetic C57BL/6 mice, respectively. All of these results demonstrated that compound26was considered to be a promising lead compound suitable for further optimization.
