奥维诺醇6,14-桥的官能化。第3部分：18-和19-羟基取代奥维诺醇的制备及药理评价。
Functionalization of the 6,14-bridge of the orvinols. Part 3: preparation and pharmacological evaluation of 18- and 19-hydroxyl substituted orvinols.
作者信息
Wu Huifang, Smith Trudy A, Huang Hongyan, Wang Jia Bei, Deschamps Jeffrey R, Coop Andrew
机构信息
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
出版信息
Bioorg Med Chem Lett. 2007 Sep 1;17(17):4829-31. doi: 10.1016/j.bmcl.2007.06.050. Epub 2007 Jun 20.
Abstract
The orvinols are a class of potent opioids which have been extensively studied, yet little is known about the effects of introducing substituents into the 18- and 19-positions. The etheno bridge of thevinone was hydroxylated to give both the 18- and 19-hydroxyl substituted thevinols. After 3-O-demethylation to the corresponding orvinols, binding and GTPgammaS functional assays indicated that hydroxyl substitution at the 18- and 19-positions differentially affects the mu opioid efficacy of orvinols.
摘要
奥维诺醇类是一类经过广泛研究的强效阿片类药物，但对于在18位和19位引入取代基的影响却知之甚少。将蒂巴因酮的乙烯桥羟基化，得到18位和19位羟基取代的奥维诺醇。在将其3-O-去甲基化转化为相应的奥维诺醇后，结合和GTPγS功能测定表明，18位和19位的羟基取代对奥维诺醇的μ阿片样物质效能有不同影响。
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