Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: Design, synthesis, structural biology, and molecular docking studies

Abstract

A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity. © 2006 American Chemical Society.