標題: Design and Structural Analysis of Novel Pharmacophores for Potent and Selective Peroxisome Proliferator-activated Receptor gamma Agonists
作者: Lin, Chia-Hui
Peng, Yi-Hui
Coumar, Mohane Selvaraj
Chittimalla, Santhosh Kumar
Liao, Chun-Chen
Lyn, Ping-Chiang
Huang, Chin-Chieh
Lien, Tzu-Wen
Lin, Wen-Hsing
Hsu, John T. -A.
Cheng, Jai-Hong
Chen, Xin
Wu, Jian-Sung
Chao, Yu-Sheng
Lee, Hwei-Jen
Juo, Chiun-Gung
Wu, Su-Ying
Hsieh, Hsing-Pang
生物科技學系
Department of Biological Science and Technology
公開日期: 23-Apr-2009
摘要: Utilizing medicinal chemistry design strategies Such as benzo splitting and ring expansion, we converted PPAR alpha/gamma dual agonist 1 to selective PPAR gamma agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPAR gamma receptor. with 80- to 100-fold PPAR gamma selectivity over PPAR alpha receptor. X-ray cocrystal studies in PPAR gamma and modeling studies in PPAR alpha give molecular insights for the improved PPAR gamma potency and selectivity for 19 when compared to 1.
URI: http://dx.doi.org/10.1021/jm801594x
http://hdl.handle.net/11536/7344
ISSN: 0022-2623
DOI: 10.1021/jm801594x
期刊: JOURNAL OF MEDICINAL CHEMISTRY
Volume: 52
Issue: 8
起始頁: 2618
結束頁: 2622
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