國家衛生研究院 NHRI:Item 3990099045/3744
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    题名: Discovery of 2-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1H-pyrazol-3-yl]-1,5,5-trimethyl-1,5-dihydro-imidazol-4-thione (BPR-890) via an active metabolite. A novel, potent and selective cannabinoid-1 receptor inverse agonist with high antiobesity efficacy in DIO mice
    作者: Wu, CH;Hung, MS;Song, JS;Yeh, TK;Chou, MC;Chu, CM;Jan, JJ;Hsieh, MT;Tseng, SL;Chang, CP;Hsieh, WP;Lin, Y;Yeh, YN;Chung, WL;Kuo, CW;Lin, CY;Shy, HS;Chao, YS;Shia, KS
    贡献者: Division of Biotechnology and Pharmaceutical Research
    摘要: By using the active metabolite 5 as an initial template, further structural modifications led to the identification of the titled compound 24 (BPR-890) as a highly potent CB1 inverse agonist possessing an excellent CB2/1 selectivity and remarkable in vivo efficacy in diet-induced obese mice with a minimum effective dose as low as 0.03 mg/kg (po qd) at the end of the 30-day chronic study. Current SAR studies along with those of many existing rimonabant-mimicking molecules imply that around the pyrazole C3-position, a rigid and deep binding pocket should exist for CB1 receptor. In addition, relative to the conventional carboxamide carbonyl, serving as a key hydrogen-bond acceptor during ligand-CB1 receptor interaction, the corresponding polarizable thione carbonyl might play a more critical role in stabilizing the Asp366-Lys192 salt bridge in the proposed CB1-receptor homology model and inducing significant selectivity for CB1R over CB2R.
    日期: 2009-07-23
    關聯: Journal of Medicinal Chemistry. 2009 Jul 23;52(14):4496-4510.
    Link to: http://dx.doi.org/10.1021/jm900471u
    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:000268139900043
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=67650714102
    显示于类别:[夏克山] 期刊論文
    [趙宇生(2002-2013)] 期刊論文
    [葉燈光] 期刊論文
    [洪明秀] 期刊論文
    [張竣評] 期刊論文

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