diethyl [5-acetamido-4-azido-6-(1,2,3-triacetoxy)propyl-4,5,6-trihydropyran-2-yl]phosphonate | 1338226-30-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: diethyl [5-acetamido-4-azido-6-(1,2,3-triacetoxy)propyl-4,5,6-trihydropyran-2-yl]phosphonate
• 英文别名: [(2R,3S)-3-[(2R,3R,4S)-3-acetamido-4-azido-6-diethoxyphosphoryl-3,4-dihydro-2H-pyran-2-yl]-2,3-diacetyloxypropyl] acetate
• CAS: 1338226-30-4
• 化学式: C₂₀H₃₁N₄O₁₁P
• 分子量: 534.46
• InChiKey: CCHXADBRYUCNHV-APQLOABGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  36
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  167
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  diethyl [5-acetamido-4-azido-6-(1,2,3-triacetoxy)propyl-4,5,6-trihydropyran-2-yl]phosphonate 在 氢气 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以278 mg的产率得到[(2R,3S)-3-[(2R,3R,4S)-3-acetamido-4-amino-6-diethoxyphosphoryl-3,4-dihydro-2H-pyran-2-yl]-2,3-diacetyloxypropyl] acetate
  参考文献：
  名称：

  A Practical Synthesis of Zanamivir Phosphonate Congeners with Potent Anti-influenza Activity

  摘要：

  Two phosphonate compounds la (4-amino-1-phosphono-DANA) and 1b (phosphono-zanamivir) are synthesized and shown More potent than zanamivir against the neuraminidases of avian and human influenza viruses, including the oseltamivir-resistant strains. For the first time, the practical synthesis of these phosphonate compounds is realized by conversion of sialic acid to peracetylated phosphono-DANA diethyl ester (5) as a key intermediate in three steps by a novel approach. In comparison with zanamivir, the high affinity of la and 1b can be partly attributable to the strong electrostatic interactions of their phosphonate,group'S With the three arginine residues (Arg118, Arg292, and Arg371) in the active site of neuraminidases. These phosphonates are nontoxic to the human 293T cells; they protect cells from influenza : virus infection with EC50 values. in low-nanomolar range; including the wild-type WSN (H1N1), the 2009 pandemic (H1N1), the oseltamivir-resistant H274Y (H1N1), RG14 (H5N1); and Udorn (H3N2) influenza strains.

  DOI：

  10.1021/ja207892q
• 作为产物：
  描述：

  diethyl [5-acetamido-4-acetoxy-6-(1,2,3-triacetoxy)propyl-4,5,6-trihydropyran-2-yl]phosphonate 在 叠氮基三甲基硅烷 、 硫酸 、 溶剂黄146 作用下， 以 叔丁醇 为溶剂， 反应 72.0h， 生成 diethyl [5-acetamido-4-azido-6-(1,2,3-triacetoxy)propyl-4,5,6-trihydropyran-2-yl]phosphonate
  参考文献：
  名称：

  A Practical Synthesis of Zanamivir Phosphonate Congeners with Potent Anti-influenza Activity

  摘要：

  Two phosphonate compounds la (4-amino-1-phosphono-DANA) and 1b (phosphono-zanamivir) are synthesized and shown More potent than zanamivir against the neuraminidases of avian and human influenza viruses, including the oseltamivir-resistant strains. For the first time, the practical synthesis of these phosphonate compounds is realized by conversion of sialic acid to peracetylated phosphono-DANA diethyl ester (5) as a key intermediate in three steps by a novel approach. In comparison with zanamivir, the high affinity of la and 1b can be partly attributable to the strong electrostatic interactions of their phosphonate,group'S With the three arginine residues (Arg118, Arg292, and Arg371) in the active site of neuraminidases. These phosphonates are nontoxic to the human 293T cells; they protect cells from influenza : virus infection with EC50 values. in low-nanomolar range; including the wild-type WSN (H1N1), the 2009 pandemic (H1N1), the oseltamivir-resistant H274Y (H1N1), RG14 (H5N1); and Udorn (H3N2) influenza strains.

  DOI：

  10.1021/ja207892q

文献信息

• ZANAMIVIR PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY AND DETERMINING OSELTAMIVIR SUSCEPTIBILITY OF INFLUENZA VIRUSES
  申请人：Wong Chi-Huey

  公开号：US20130225532A1

  公开（公告）日：2013-08-29

  Methods and compositions for detection of drug resistant pathogens and treatment against infections thereof are provided. Methods for detection of oseltamivir-resistant influenza viruses by competitive binding assays utilizing non-oseltamivir influenza virus neuraminidase inhibitors and oseltamivir carboxylate are provided. Influenza virus neuraminidase inhibitors coupled to sensors and useful for employment in the methods of the invention are disclosed. Novel phosphonate compounds active as neuraminidase inhibitors against wild-type and oseltamivir-resistant influenza strains of H1N1, H5N1 and H3N2 viruses are disclosed. An enantioselective synthetic route to preparation of these phosphonate compounds via sialic acid is provided.

  本发明提供了检测耐药病原体和治疗感染的方法和组合物。本发明提供了利用非奥司他韦流感病毒神经氨酸酶抑制剂和奥司他韦羧酸盐进行竞争结合测定的检测奥司他韦耐药性流感病毒的方法。本发明还揭示了与传感器耦合并在本发明方法中使用的流感病毒神经氨酸酶抑制剂。本发明还揭示了对H1N1、H5N1和H3N2病毒的野生型和奥司他韦耐药株具有神经氨酸酶抑制剂活性的新型膦酸酯化合物。本发明还提供了通过唾液酸的对映选择性合成途径制备这些膦酸酯化合物的方法。
• ZANAMIVIR PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY AND DETERMINING OSELTAMIVIR SUSCEPTIBILITY OF INFLUENZA VIRUSES
  申请人：Academia Sinica

  公开号：EP2975409A1

  公开（公告）日：2016-01-20

  Methods and compositions for detection of drug resistant pathogens and treatment against infections thereof are provided. Methods for detection of oseltamivir-resistant influenza viruses by competitive binding assays utilizing non-oseltamivir influenza virus neuraminidase inhibitors and oseltamivir carboxylate are provided. Influenza virus neuraminidase inhibitors coupled to sensors and useful for employment in the methods of the invention are disclosed. Novel phosphonate compounds active as neuraminidase inhibitors against wild-type and oseltamivir-resistant influenza strains of H1N1, H5N1 and H3N2 viruses are disclosed. An enantioselective synthetic route to preparation of these phosphonate compounds via sialic acid is provided.

  提供了检测耐药病原体和治疗其感染的方法和组合物。本发明提供了通过利用非奥司他韦流感病毒神经氨酸酶抑制剂和奥司他韦羧酸盐的竞争性结合测定来检测抗奥司他韦流感病毒的方法。本发明公开了与传感器结合并可用于本发明方法的流感病毒神经氨酸酶抑制剂。本发明公开了新型膦酸盐化合物，作为神经氨酸酶抑制剂对野生型和抗奥司他韦的 H1N1、H5N1 和 H3N2 流感病毒株具有活性。本发明提供了通过硅烷酸制备这些膦酸盐化合物的对映体选择性合成路线。
• US9403855B2
  申请人：——

  公开号：US9403855B2

  公开（公告）日：2016-08-02