Discovery of gemfibrozil analogues that activate PPARalpha and enhance the expression of gene CPT1A involved in fatty acids catabolism.

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De Filippis B, Giancristofaro A, Ammazzalorso A, D'Angelo A, Fantacuzzi M, Giampietro L, Maccallini C, Petruzzelli M, Amoroso R

Discovery of gemfibrozil analogues that activate PPARalpha and enhance the expression of gene CPT1A involved in fatty acids catabolism.

Eur J Med Chem. 2011 Oct;46(10):5218-24. doi: 10.1016/j.ejmech.2011.08.022. Epub 2011 Aug 23.

PubMed ID

21889235 [ View in PubMed

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Abstract

A new series of gemfibrozil analogues conjugated with alpha-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPARalpha agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPARalpha receptor and were also screened for their activity on PPARalpha-regulated gene CPT1A.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Gemfibrozil	Peroxisome proliferator-activated receptor alpha	EC 50 (nM)	59000	N/A	N/A	Details