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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/3386
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| Title: | Bioisosteric replacement of the pyrazole 5-aryl moiety of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A novel series of alkynylthiophenes as potent and selective cannabinoid-1 receptor antagonists |
| Authors: | Tseng, SL;Hung, MS;Chang, CP;Song, JS;Tai, CL;Chiu, HH;Hsieh, WP;Lin, Y;Chung, WL;Kuo, CW;Wu, CH;Chu, CM;Tung, YS;Chao, YS;Shia, KS |
| Contributors: | Division of Biotechnology and Pharmaceutical Research |
| Abstract: | Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the 2-thienyl moiety appended with an appropriate alkynyl unit, a novel class of 5-(5-alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB1/2 selectivity, was discovered, many of which, as typified by compound 18, showed significant weight reduction in diet-induced obese mouse model, thus pharmacologically validating that the bioisosteric replacement described above is viable. Also encouraging was the finding that a subtle structural modification of the newly developed series could result in a distinct difference in the intrinsic property, as demonstrated by compounds 12 (NA) and its methylated structural isomers 15 (PA) and 18 (IA). Moreover, current structure-activity relationship studies revealed that around the pyrazole 5-position of 1, a deep and flat crevice surrounded by a sequence of hydrophobic/aromatic residues as indicated by the CB1-receptor homology model might exist in the binding site. |
| Date: | 2008-09-11 |
| Relation: | Journal of Medicinal Chemistry. 2008 Sep 11;51(17):5397-5412. |
| Link to: | http://dx.doi.org/10.1021/jm800066v |
| 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:000258979600020 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=51849098198 |
| Appears in Collections: | [夏克山] 期刊論文
[趙宇生(2002-2013)] 期刊論文
[洪明秀] 期刊論文
[張竣評] 期刊論文
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| SCP51849098198.pdf | | 513Kb | Adobe PDF | 879 | View/Open |
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