Synthesis, biological evaluation and molecular investigation of fluorinated peroxisome proliferator-activated receptors alpha/gamma dual agonists

PPARs are transcription factors that govern lipid and glucose homeostasis and play a central role in cardiovascular decease, obesity, and diabetes. Thus, there is significant interest in developing new agonists for these receptors. Given that the introduction of fluorine generally has a profound effect on the physical and/or biological properties of the target molecule, we synthesized a series of fluorinated analogs of the previously reported compound 2, some of which turned out to be remarkable PPARalpha and PPARgamma dual agonists. Docking experiments were also carried out to gain insight into the interactions of the most active derivatives with both receptors