N-pentafluorobenzyl-1-deoxynojirimycin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-pentafluorobenzyl-1-deoxynojirimycin
• 英文别名: (2R,3R,4R,5S)-2-(hydroxymethyl)-1-[(2,3,4,5,6-pentafluorophenyl)methyl]piperidine-3,4,5-triol
• 化学式: C₁₃H₁₄F₅NO₄
• 分子量: 343.25
• InChiKey: VYPGXPLGHYHIRV-PLSZNQMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  84.2
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-脱氧野尻霉素 、 alkaline earth salt of/the/ methylsulfuric acid 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以67%的产率得到N-pentafluorobenzyl-1-deoxynojirimycin
  参考文献：
  名称：

  Specific inhibition effects of N -pentafluorobenzyl-1-deoxynojirimycin on human CD4+ T cells

  摘要：

  We first synthesized N-pentafluorobenzyl-1-deoxynojirimycin (5F-DNM), one new derivative of 1-deoxynojirimycin (DNM). Effects on human peripheral blood mononuclear cells (PMBC) and secretion of cytokines from human PBMC by 5F-DNM were investigated. It was first found that 5F-DNM remarkably inhibited the secretion of interleukin-4 (IL-4) and had a specific inhibition on the expression of CD4 molecules. 5F-DNM, much less toxic than cyclosporin A, might be used as a new candidate of immunosuppressant for specifically treating Th2-mediated immune diseases. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.092

文献信息

• An iminosugar N-pentafluorobenzyl-1-deoxynojirimycin as a novel potential immunosuppressant for the treatment of Th2-related diseases
  作者：Min Liu、Shaoru Wang、Yi-Dan Zhou、Tian Xiang、Huifen Dong、Kun Yang、Xiao-Lian Zhang

  DOI：10.1016/j.bmcl.2011.10.081

  日期：2012.1

  Increased levels of Th2 cytokine interleukin-4 (IL-4) have been reported to be involved in the pathogenesis of the parasite Schistosoma japonicum (S. japonicum) infection or detected in the serum of the causative agent of acquired immunodeficiency syndrome (AIDS) patients. This correlates with a worsened outcome of AIDS. The inhibition of a Th2 type response might aid in the treatment of these Th2-related diseases. Previously, we found that N-pentafluorobenzyl-1-deoxynojirimycin (5F-DNM), a new derivative of 1-deoxynojirimycin (DNM) (an inhibitor of the glycoprotein processing enzymes, glucosidase I and II), had specific inhibition effects on human CD4(+) T cells. In this study, we further found that 5F-DNM not only markedly inhibited in vitro IL-4 production from human PBMCs, CD4(+) T cells and mouse splenocytes but also strongly inhibited the production of IL-4 in splenocytes from a mouse model of S. japonicum infection. The numbers of S. japonicum worms were significantly decreased in vivo upon the treatment of mice with 5F-DNM. We demonstrated the mechanism of 5F-DNM effects on CD4(+) T cells acts via the inhibition of the IL-4/JAK1/STAT6 signaling pathway. Moreover, 5F-DNM was found to induce CD4 internalization (transfer from the cellular surface to the cytoplasm) in CD4(+) T cells and had no significant effects on the overall expression levels of CD4. These findings indicate that 5F-DNM might be used as a potential candidate for the treatment of S. japonicum parasitic infection, AIDS and other Th2-related diseases. (C) 2011 Elsevier Ltd. All rights reserved.