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

作者：De Filippis Barbara; Giancristofaro Antonella; Ammazzalorso Alessandra; D'Angelo Alessandra; Fantacuzzi Marialuigia; Giampietro Letizia; Maccallini Cristina; Petruzzelli Michele; Amoroso Rosa^*

来源：European Journal of Medicinal Chemistry, 2011, 46(10): 5218-5224.

DOI：10.1016/j.ejmech.2011.08.022

• Nuclear receptors modulators
• PPAR alpha
• Analogues of gemfibrozil
• Stilbene
• Fibrates

A new series of gemfibrozil analogues conjugated with alpha-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPAR alpha 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 PPAR alpha receptor and were also screened for their activity on PPAR alpha-regulated gene CPT1A.

• 出版日期2011-10