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: | 23-四月-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 |
顯示於類別: | 期刊論文 |