4'-叠氮胸苷类似物和4'-叠氮-2'-脱氧-5-甲基胞苷类似物的抗乙型肝炎病毒活性的合成与评价：新型抗HBV药物开发的结构见解
Synthesis and evaluation of the anti-hepatitis B virus activity of 4'-Azido-thymidine analogs and 4'-Azido-2'-deoxy-5-methylcytidine analogs: structural insights for the development of a novel anti-HBV agent.
作者信息
Onitsuka Kengo, Tokuda Ryoh, Kuwata-Higashi Nobuyo, Kumamoto Hiroki, Aoki Manabu, Amano Masayuki, Kohgo Satoru, Das Debananda, Haraguchi Kazuhiro, Mitsuya Hiroaki, Imoto Shuhei
机构信息
Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2020;39(4):518-529. doi: 10.1080/15257770.2019.1664749. Epub 2019 Sep 12.
Hepatitis B virus (HBV) infection is a major worldwide health problem that requires the development of improved antiviral therapies. Here, a series of 4'-Azido-thymidine/4'-Azido-2'-deoxy-5-methylcytidine derivatives (, ) were synthesized, and their anti-HBV activities evaluated. Compounds were synthesized via an SAr reaction of , in which the 4-position of the thymine moiety was activated as the 2,4,6-triisopropylbenzenesulfonate. Compounds showed no antiviral activity. However, 4'-Azido thymidine () and 4'-Azido-2'-deoxy-5-methylcytidine () displayed significant anti-HBV activity (EC = 0.63 and 5.99 M, respectively) with no detectable cytotoxicity against MT-2 cells up to 100 M.
乙型肝炎病毒（HBV）感染是一个全球性的主要健康问题，需要开发更好的抗病毒疗法。在此，合成了一系列4'-叠氮胸苷/4'-叠氮-2'-脱氧-5-甲基胞苷衍生物（，），并评估了它们的抗HBV活性。化合物通过的SAr反应合成，其中胸腺嘧啶部分的4位被激活为2,4,6-三异丙基苯磺酸盐。化合物没有显示出抗病毒活性。然而，4'-叠氮胸苷（）和4'-叠氮-2'-脱氧-5-甲基胞苷（）表现出显著的抗HBV活性（EC分别为0.63和5.99μM），在高达100μM时对MT-2细胞没有可检测到的细胞毒性。
Zotero 插件