國家衛生研究院 NHRI:Item 3990099045/3386

NHRI > Institute of Biotechnology and Pharmaceutical Research > Kak-Shan Shia > Periodical Articles > Item 3990099045/3386

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3386

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:	[Kak-Shan Shia] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles [Ming-Shiu Hung] Periodical Articles [Chun-Ping Chang] Periodical Articles

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