Fibrate-derived N-(methylsulfonyl)amides with antagonistic properties on PPARα

被引：23

作者：

Ammazzalorso, Alessandra ^{[1
]}

D'Angelo, Alessandra ^{[1
]}

Giancristofaro, Antonella ^{[1
]}

De Filippis, Barbara ^{[1
]}

Di Matteo, Mauro ^{[1
]}

Fantacuzzi, Marialuigia ^{[1
]}

Giampietro, Letizia ^{[1
]}

Linciano, Pasquale ^{[1
]}

Maccallini, Cristina ^{[1
]}

Amoroso, Rosa ^{[1
]}

机构：

[1] Univ G DAnnunzio, Dipartimento Farm, I-66100 Chieti, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 58卷

关键词：

PPARs; PPAR antagonist; Transactivation assay; FRET; PROLIFERATOR-ACTIVATED-RECEPTORS; NUCLEAR RECEPTORS; ENERGY-TRANSFER; GAMMA; AGONISTS; FAMILY; LIGAND; FUTURE; CELLS; FAT;

D O I：

10.1016/j.ejmech.2012.10.019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The identification of novel PPAR ligands represents an attractive research to fully understand the complex biological pathways regulated by these receptors. Selective PPAR modulators, inverse agonists and antagonists of three PPAR isoforms could help to clarify biological effects on lipid and glucose homeostasis. Here we describe the identification of a group of N-(methylsulfonyl)amides, derived from PPAR alpha agonist carboxylic acids. Transactivation and FRET assay confirmed an antagonist behaviour on PPAR alpha for some of these compounds, with submicromolar IC50. A preliminary analysis on selectivity alpha/gamma revealed different profiles of inhibition or activation. (C) 2012 Published by Elsevier Masson SAS.

引用

页码：317 / 322

页数：6

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