Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor γ agonists

Chia Hui Lin, Yi Hui Peng, Mohane Selvaraj Coumar, Santhosh Kumar Chittimalla, Chun Chen Liao, Ping Chiang Lyn, Chin Chieh Huang, Tzu Wen Lien, Wen Hsing Lin, John T.A. Hsu, Jai Hong Cheng, Xin Chen, Jian Sung Wu, Yu Sheng Chao, Hwei Jen Lee, Chiun Gung Juo, Su Ying Wu, Hsing Pang Hsieh

研究成果: Article同行評審

19 引文 斯高帕斯(Scopus)

摘要

Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARα/γ dual agonist 1 to selective PPARα agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARγ receptor, with 80- to 100-fold PPARγ selectivity over PPARα receptor. X-ray cocrystal studies in PPARγ and modeling studies in PPARα give molecular insights for the improved PPARγ potency and selectivity for 19 when compared to 1.

原文English
頁(從 - 到)2618-2622
頁數5
期刊Journal of Medicinal Chemistry
52
發行號8
DOIs
出版狀態Published - 2009 四月 23

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 藥物發現

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