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Synthesis, Activity, and Docking Study of Novel Phenylthiazole‐Carboxamido Acid Derivatives as FFA2 Agonists
Author(s) -
Ma Liang,
Wang Taijin,
Shi Min,
Fu Ping,
Pei Heying,
Ye Haoyu
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12729
Subject(s) - chemistry , docking (animal) , agonist , stereochemistry , antagonist , propionate , fatty acid , g protein coupled receptor , receptor , biochemistry , medicine , nursing
Free fatty acid receptor 2 ( FFA 2), also known as GPR 43, is activated by short‐chain fatty acids ( SCFA s) that are mainly produced by the gut microbiota through the fermentation of undigested carbohydrates and dietary fibers. FFA 2 currently appears to be a potential target in the management of obesity, diabetes, inflammatory diseases, and cancer. In the study, a series of novel phenylthiazole‐carboxamido acid derivatives has been synthesized and evaluated as potential orthosteric FFA 2 ligands for the study of structure–activity relationships. Compound 6e was found to exhibit the twofold potent agonistic activity in the stable hFFA 2‐transfected CHO ‐K1 cells ( EC 50 = 23.1 μ m ) as that of positive control propionate ( EC 50 = 43.3 μ m ). We also reported the results of mutagenesis studies based on the crystal structure of hFFA 1 bound to TAK ‐875 at 2.3 Å resolution to identify important residues for orthosteric agonist 6e inducing FFA 2 activation.