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http://ir.nhri.org.tw/handle/3990099045/1256
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| Title: | Novel indole-based peroxisome proliferator-activated receptor agonists: Design, SAR, structural biology, and biological activities |
| Authors: | Mahindroo, N;Huang, CF;Peng, YH;Wang, CC;Liao, CC;Lien, TW;Chittimalla, SK;Huang, WJ;Chai, CH;Prakash, E;Chen, CP;Hsu, TA;Peng, CH;Lu, IL;Lee, LH;Chang, YW;Chen, WC;Chou, YC;Chen, CT;Goparaju, CMV;Chen, YS;Lan, SJ;Yu, MC;Chen, X;Chao, YS;Wu, SY;Hsieh, HP |
| Contributors: | Division of Biotechnology and Pharmaceutical Research |
| Abstract: | The synthesis and structure-activity relationship studies of novel indole derivatives as peroxisome proliferator-activated receptor (PPAR) agonists are reported. Indole, a druglike scaffold, was studied as a core skeleton for the acidic head part of PPAR agonists. The structural features (acidic head, substitution on indole, and linker) were optimized first, by keeping benzisoxazole as the tail part, based on binding and functional activity at PPAR gamma protein. The variations in the tail part, by introducing various heteroaromatic ring systems, were then studied. In vitro evaluation led to identification of a novel series of indole compounds with a benzisoxazole tail as potent PPAR agonists with the lead compound 14 (BPR1H036) displaying an excellent pharmacokinetic profile in BALB/c mice and an efficacious glucose lowering activity in KKA(y) mice. Structural biology studies of 14 showed that the indole ring contributes strong hydrophobic interactions with PPAR gamma and could be an important moiety for the binding to the protein. |
| Keywords: | Chemistry, Medicinal |
| Date: | 2005-12-29 |
| Relation: | Journal of Medicinal Chemistry. 2005 Dec;48(26):8194-8208. |
| Link to: | http://dx.doi.org/10.1021/jm0506930 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000234301800012 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=29744432852 |
| Appears in Collections: | [謝興邦] 期刊論文
[伍素瑩] 期刊論文
[徐祖安] 期刊論文
[趙宇生(2002-2013)] 期刊論文
[陳新(2002-2015)] 期刊論文
[陳炯東] 期刊論文
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| 000234301800012.pdf | | 484Kb | Adobe PDF | 525 | View/Open |
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