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

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Fracchiolla G, Laghezza A, Piemontese L, Parente M, Lavecchia A, Pochetti G, Montanari R, Di Giovanni C, Carbonara G, Tortorella P, Novellino E, Loiodice F

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

Bioorg Med Chem. 2012 Mar 15;20(6):2141-51. doi: 10.1016/j.bmc.2012.01.025. Epub 2012 Jan 28.

PubMed ID

22341573 [ View in PubMed

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Abstract

PPARs are transcription factors that govern lipid and glucose homeostasis and play a central role in cardiovascular disease, 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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(2S)-2-(4-chlorophenoxy)-3-phenylpropanoic acid	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	9600	N/A	N/A	Details
Pioglitazone	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	570	N/A	N/A	Details