ethyl (2R)-2-[[[(2S,3S,5S)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-phenoxyphosphoryl]amino]-3-methylbutanoate | 1256632-55-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: ethyl (2R)-2-[[[(2S,3S,5S)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-phenoxyphosphoryl]amino]-3-methylbutanoate
• CAS: 1256632-55-9
• 化学式: C₂₃H₃₁N₆O₈P
• 分子量: 550.508
• InChiKey: WXLZMSDZLCVCSU-WUQXMBEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  phenyl (ethoxy-L-valinyl)phosphorochloridate 、 alpha-3'-azido-2',3'-dideoxythymidine 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 以52%的产率得到ethyl (2R)-2-[[[(2S,3S,5S)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-phenoxyphosphoryl]amino]-3-methylbutanoate
  参考文献：
  名称：

  Potential application of thymidylate kinase in nucleoside analogue activation in Plasmodium falciparum

  摘要：

  Plasmodium falciparum thymidylate kinase (PfTMPK) shows a broad range of substrate tolerance when compared to the corresponding human enzyme. Besides 2'-deoxythymidine monophosphate (dTMP), PfTMPK can phosphorylate 3'-azido-2',3'-dideoxythymidine monophosphate (AZTMP) very efficiently. In contrast, human thymidylate kinase (hTMPK) is 200 times less active towards AZTMP. We were interested to see if we could use PfTMPK to activate 3'-azido-2',3'-deoxythymidine (AZT) derivatives as a strategy to treat malaria. P. falciparum lacks a pyrimidine nucleoside kinase which usually activates nucleoside and nucleoside analogues to the corresponding monophosphates. Therefore, several prodrug analogues of AZT and related nucleoside monophosphates were prepared and analysed for antiparasitic activity. The prodrugs showed an increase in activity over the parent nucleoside analogues, which showed no inhibition of parasite growth at the concentration tested. The evidence here reported provides a strategy that could be exploited for further anti-malarial design. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.006

文献信息

• Potential application of thymidylate kinase in nucleoside analogue activation in Plasmodium falciparum
  作者：Huaqing Cui、Luis M. Ruiz-Pérez、Dolores González-Pacanowska、Ian H. Gilbert

  DOI：10.1016/j.bmc.2010.07.006

  日期：2010.10.15

  Plasmodium falciparum thymidylate kinase (PfTMPK) shows a broad range of substrate tolerance when compared to the corresponding human enzyme. Besides 2'-deoxythymidine monophosphate (dTMP), PfTMPK can phosphorylate 3'-azido-2',3'-dideoxythymidine monophosphate (AZTMP) very efficiently. In contrast, human thymidylate kinase (hTMPK) is 200 times less active towards AZTMP. We were interested to see if we could use PfTMPK to activate 3'-azido-2',3'-deoxythymidine (AZT) derivatives as a strategy to treat malaria. P. falciparum lacks a pyrimidine nucleoside kinase which usually activates nucleoside and nucleoside analogues to the corresponding monophosphates. Therefore, several prodrug analogues of AZT and related nucleoside monophosphates were prepared and analysed for antiparasitic activity. The prodrugs showed an increase in activity over the parent nucleoside analogues, which showed no inhibition of parasite growth at the concentration tested. The evidence here reported provides a strategy that could be exploited for further anti-malarial design. (C) 2010 Elsevier Ltd. All rights reserved.