Synthesis and Biological Activities of Novel GPR40 Agonists
HUANG Jing1,2， GUO Bin2， ZHOU Xian-li1
1. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Abstract：Methyl 2-｛6-［4-(tert-butyldimethylsilyloxy)but-2-ynyloxy］-2,3-dihydrobenzofuran-3-yl｝acetate（3） was prepared by protection of 2-butyne-1,4-diol with tertbutyldimethylsilyl chloride, then Mitsunobu reaction with methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetate. Six novel benzo-dihydrofuran derivatives(7a~7f) were synthesized by deprotection, Mitsunobu reaction with phenol derivatives and hydrolysis from 3. The structures were characterized by 1H NMR， 13C NMR and HR-EI-MS. The activities of 7a~7f were tested in GPR40- transfected HEK293 cells. The results showed that 7a~7f all exhibited agonistic activities on GPR40, 7e and 7f were the most potent componds, with the EC50 of 0.593 μmol·L-1 and 0.596 μmol·L-1, respectively.
2016, Vol. 24 
