3'-azido-3',5'-dideoxythymidine 5'-β,γ-imidotriphosphate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3'-azido-3',5'-dideoxythymidine 5'-β,γ-imidotriphosphate
• 英文别名: [[[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl-hydroxy-phosphoryl]oxy-hydroxy-phosphoryl]amino]phosphonic acid；[[[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl-hydroxyphosphoryl]oxy-hydroxyphosphoryl]amino]phosphonic acid
• 化学式: C₁₀H₁₇N₆O₁₁P₃
• 分子量: 490.2
• InChiKey: MDZWDSAGTVRGLZ-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  226
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  [(2S,3S,5R)-3-Azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl]-imidazol-1-yl-phosphinic acid 在 六甲基磷酰三胺 、 tetrakis(tributylammonium) imidodiphosphate 作用下， 反应 4.0h， 生成 3'-azido-3',5'-dideoxythymidine 5'-β,γ-imidotriphosphate
  参考文献：
  名称：

  Synthesis of 5'-Triphosphate Mimics (P3Ms) of 3'-Azido-3',5'-Dideoxythymidine and 3',5'-Dideoxy-5'-Difluoromethylenethymidine as HIV-1 Reverse Transcriptase Inhibitors

  摘要：

  3'-Azido-3,5-dideoxythymidine 5-phosphonate and 3',5-dideoxy-5-difluoromethylenethymidine 5'-phosphonate were prepared by multistep syntheses. The nucleoside 5-phosphonates were converted to their triphosphates and triphosphate mimics (P3Ms) containing beta,gamma-difluoromethylene, beta,gamma-dichloromethylene, or beta,gamma-imodo by condensation with pyrophosphate or Pyrophosphate mimics, respectively. Inhibition of HIV-1 reverse transcriptase by the nucleoside P3Ms is briefly discussed.

  DOI：

  10.1081/ncn-200055707

文献信息

• Nucleotide mimics and their prodrugs
  申请人：——

  公开号：US20040059104A1

  公开（公告）日：2004-03-25

  The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

  本发明涉及核苷酸二磷酸类似物和核苷酸三磷酸类似物，其包含二磷酸或三磷酸基团类似物和可选的糖修饰和/或碱基修饰。本发明中的核苷酸类似物，以药学上可接受的盐、药学上可接受的前药或制剂形式，可用作抗病毒、抗微生物和抗癌剂。本发明提供了一种治疗病毒感染、微生物感染和增生性疾病的方法。本发明还涉及包含本发明化合物的药物组合物，可选地与其他药学活性剂组合使用。
• Synthesis of 5'-Triphosphate Mimics (P3Ms) of 3'-Azido-3',5'-Dideoxythymidine and 3',5'-Dideoxy-5'-Difluoromethylenethymidine as HIV-1 Reverse Transcriptase Inhibitors
  作者：Vivek Rajwanshi、Marija Prhavc、Patrick Fagan、Jennifer Brooks、Tiffany Hurd、P. Dan Cook、Guangyi Wang

  DOI：10.1081/ncn-200055707

  日期：2005.3.1

  3'-Azido-3,5-dideoxythymidine 5-phosphonate and 3',5-dideoxy-5-difluoromethylenethymidine 5'-phosphonate were prepared by multistep syntheses. The nucleoside 5-phosphonates were converted to their triphosphates and triphosphate mimics (P3Ms) containing beta,gamma-difluoromethylene, beta,gamma-dichloromethylene, or beta,gamma-imodo by condensation with pyrophosphate or Pyrophosphate mimics, respectively. Inhibition of HIV-1 reverse transcriptase by the nucleoside P3Ms is briefly discussed.