國家衛生研究院 NHRI:Item 3990099045/9983
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 12145/12927 (94%)
造访人次 : 909226      在线人数 : 801
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧：
  • 您可在西文检索词汇前后加上"双引号"，以获取较精准的检索结果
  • 若欲以作者姓名搜寻，建议至进阶搜寻限定作者字段，可获得较完整数据
    •  进阶搜寻
    主页 ‧ 登入 ‧ 上传 ‧ 说明 ‧ 关于NHRI ‧ 管理 到手机版


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/9983


    题名: Discovery, structure-activity relationship studies, and anti-nociceptive effects of N-(1,2,3,4-tetrahydro-1-isoquinolinylmethyl)benzamides as novel opioid receptor agonists
    作者: Chen, SR;Ke, YY;Yeh, TK;Lin, SY;Ou, LC;Chen, SC;Chang, WT;Chang, HF;Wu, ZH;Hsieh, CC;Law, PY;Loh, HH;Shih, C;Lai, YK;Yeh, SH;Ueng, SH
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects. In this study, we identified N-({2-[(4-bromo-2-trifluoromethoxyphenyl)sulfonyl]-1,2,3,4-tetrahydro-1-isoquinolinyl}methyl)cyclohexanecarboxamide (1) as a novel opioid receptor agonist by high-throughput screening. Structural modifications made to 1 to improve potency and blood-brain-barrier (BBB) penetration resulted in compounds 45 and 46. Compound 45 was a potent MOR/KOR (κ-opioid receptor) agonist, and compound 46 was a potent MOR and medium KOR agonist. Both 45 and 46 demonstrated a significant anti-nociceptive effect in a tail-flick test performed in wild type (WT) B6 mice. The ED50 value of 46 was 1.059 mg/kg, and the brain concentrations of 45 and 46 were 7424 and 11696 ng/g, respectively. Accordingly, compounds 45 and 46 are proposed for lead optimization and in vivo disease-related pain studies.
    日期: 2017-01
    關聯: European Journal of Medicinal Chemistry. 2017 Jan;126:202-217.
    Link to: http://dx.doi.org/10.1016/j.ejmech.2016.09.003
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0223-5234&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000396804600020
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84992549305
    显示于类别:[翁紹華] 期刊論文
    [葉修華] 期刊論文
    [石全(2014-2017)] 期刊論文
    [葉燈光] 期刊論文
    [林書玉] 期刊論文

    文件中的档案:

    档案 描述 大小格式浏览次数
    SDO0223523416307310.pdf.pdf1858KbAdobe PDF686检视/开启


    在NHRI中所有的数据项都受到原著作权保护.

    TAIR相关文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回馈