Indol-1-yl Acetic Acids as Peroxisome Proliferator-Activated Receptor Agonists: Design, Synthesis, Structural Biology, and Molecular Docking Studies

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 PPARgamma protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARgamma protein resulting in potent activity.