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

  • J Med Chem. 2006 Feb 9;49(3):1212-6. doi: 10.1021/jm0510373.
Neeraj Mahindroo  1 ,  Chiung-Chiu Wang ,  Chun-Chen Liao ,  Chien-Fu Huang ,  I-Lin Lu ,  Tzu-Wen Lien ,  Yi-Huei Peng ,  Wei-Jan Huang ,  Ying-Ting Lin ,  Ming-Chen Hsu ,  Chia-Hui Lin ,  Chia-Hua Tsai ,  John T-A Hsu ,  Xin Chen ,  Ping-Chiang Lyu ,  Yu-Sheng Chao ,  Su-Ying Wu ,  Hsing-Pang Hsieh
Affiliations
  • 1. Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
PMID: 16451087 DOI: 10.1021/jm0510373
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 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.