tocopheryl-deoxynojirimycin

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: tocopheryl-deoxynojirimycin
• 英文别名: Top-DNJ；tocopheryl-DNJ；(2R,3R,4R,5S)-2-(hydroxymethyl)-1-[5-[[(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl]oxy]pentyl]piperidine-3,4,5-triol
• 化学式: C₄₀H₇₁NO₆
• 分子量: 662.007
• InChiKey: QBVNNAXOIBYUCJ-NEBIYWLMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10
• 重原子数：
  47
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  天然维生素E 在 sodium methylate 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 对甲苯磺酸 、 溶剂黄146 、 sodium sulfate 作用下， 以 甲醇 、 水 为溶剂， 生成 tocopheryl-deoxynojirimycin
  参考文献：
  名称：

  ToP-DNJ, a Selective Inhibitor of Endoplasmic Reticulum α-Glucosidase II Exhibiting Antiflaviviral Activity

  摘要：

  Iminosugars have therapeutic potential against a range of diseases, due to their efficacy as glycosidase inhibitors. A major challenge in the development of iminosugar drugs lies in making a compound that is selective for the glycosidase associated with a given disease. We report the synthesis of ToP-DNJ, an antiviral iminosugar tocopherol conjugate. Tocopherol was incorporated into the design of the iminosugar in order to direct the drug to the liver and immune cells, specific tissues of interest for antiviral therapy. ToP-DNJ inhibits ER a-glucosidase II at low micromolar concentrations and selectively accumulates in the liver in vivo. In cellular assays, the drug showed efficacy exclusively in immune cells of the myeloid lineage. Taken together, these data demonstrate that inclusion of a native metabolite into an iminosugar provides selectivity with respect to target enzyme, target cell, and target tissue.

  DOI：

  10.1021/acschembio.7b00870

文献信息

• NOVEL IMINOSUGARS AND THEIR APPLICATIONS
  申请人：The Chancellor, Masters and Scholars of the University of Oxford

  公开号：US20130331578A1

  公开（公告）日：2013-12-12

  Iminosugar compounds are described that have inbuilt delivery features by virtue of covalent incorporation of a tocopherol moiety, or alternative moieties that are analogues of tocopherol or select analogues of cholesterol, or its antagonist “Ezitimibe”; and are likely to have broad spectrum antiviral activity. The compounds differ from previous iminosugar compounds, even lipophillic ones, being more hydrophobic and resembling fats and oils in their partition behavior in vivo into lipid phases of lipoproteins, cellular lipid droplet organelles and biological membranes. These features confer a number of unique delivery attributes in vivo, favorable to the therapy of virus infections involving cells of the lymphoid system and the liver, in particular, but these features are also favorable in general for the treatment of virus infections of man and animals.

  本文描述了一类具有内置传递特性的伊米诺糖化合物，这是由于共价结合了生育酚基团或生育酚类似物或选择性胆固醇类似物或其拮抗剂“依贝普利”而实现的，并且可能具有广谱的抗病毒活性。这些化合物与以前的伊米诺糖化合物不同，即使是亲脂性的化合物，也更具亲水性，并且在体内分配到脂蛋白、细胞脂滴器官和生物膜的脂质相中，类似于脂肪和油。这些特征在体内具有许多独特的传递属性，有利于淋巴系统和肝脏细胞感染病毒的治疗，特别是对于人和动物的病毒感染治疗也是有利的。
• GLYCOLIPID INHIBITION USING IMINOSUGARS
  申请人：UNITHER VIROLOGY, LLC

  公开号：US20160075651A1

  公开（公告）日：2016-03-17

  The application provides iminosugars with a high activity and specificity for inhibiting ceramide glucosyltransferase.
• US8921568B2
  申请人：——

  公开号：US8921568B2

  公开（公告）日：2014-12-30
• ToP-DNJ, a Selective Inhibitor of Endoplasmic Reticulum α-Glucosidase II Exhibiting Antiflaviviral Activity
  作者：J. L. Kiappes、Michelle L. Hill、Dominic S. Alonzi、Joanna L. Miller、Ren Iwaki、Andrew C. Sayce、Alessandro T. Caputo、Atsushi Kato、Nicole Zitzmann

  DOI：10.1021/acschembio.7b00870

  日期：2018.1.19

  Iminosugars have therapeutic potential against a range of diseases, due to their efficacy as glycosidase inhibitors. A major challenge in the development of iminosugar drugs lies in making a compound that is selective for the glycosidase associated with a given disease. We report the synthesis of ToP-DNJ, an antiviral iminosugar tocopherol conjugate. Tocopherol was incorporated into the design of the iminosugar in order to direct the drug to the liver and immune cells, specific tissues of interest for antiviral therapy. ToP-DNJ inhibits ER a-glucosidase II at low micromolar concentrations and selectively accumulates in the liver in vivo. In cellular assays, the drug showed efficacy exclusively in immune cells of the myeloid lineage. Taken together, these data demonstrate that inclusion of a native metabolite into an iminosugar provides selectivity with respect to target enzyme, target cell, and target tissue.