5-fluoro-2'-deoxyuridine-5'-O-[1-naphthyl(tetrahydropyroxy-L-alaninyl)]phosphate | 1338052-37-1

• 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: 5-fluoro-2'-deoxyuridine-5'-O-[1-naphthyl(tetrahydropyroxy-L-alaninyl)]phosphate
• 英文别名: 5-fluoro-2'-deoxyuridine-5'-O-[1-naphthyl(tetrahydropyroy-L-alaninyl)] phosphate；5-fluoro-2'-deoxyuridine-5'-O-[1-naphthyl-(tetrahydropyroxy-L-alaninyl)] phosphate；oxan-4-yl (2S)-2-[[[(2R,3S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate
• CAS: 1338052-37-1
• 化学式: C₂₇H₃₁FN₃O₁₀P
• 分子量: 607.529
• InChiKey: GTRLZDWIXZKLGN-GVZMXMMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (2S)-tetrahydro-2H-pyran-4-yl 2-(chloro(naphthalene-1-yloxy)phosphorylamino)propanoate 、 5-氟-2'-脱氧脲核苷 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以1.6%的产率得到5-fluoro-2'-deoxyuridine-5'-O-[1-naphthyl(tetrahydropyroxy-L-alaninyl)]phosphate
  参考文献：
  名称：

  Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside

  摘要：

  The fluorinated pyrimidine family of nucleosides continues to represent major current chemotherapeutic agents for treating solid tumors. We herein report their phosphate prodrugs, ProTides, as promising new derivatives, which partially bypass the dependence of the current drugs on active transport and nucleoside kinase-mediated activation. They are also resistant to metabolic deactivation by phosphorolytic enzymes. We report 39 ProTides of the fluorinated pyrimidine FUDR with variation in the aryl, ester, and amino acid. regions. Notably, only certain ProTide motifs are successful in delivering the nucleoside monophosphate into intact cells. We also find that the ProTides retain activity in mycoplasma infected cells, unlike FUDR. Data suggest these compounds to be worthy of further progression.

  DOI：

  10.1021/jm200815w

文献信息

• Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside
  作者：Christopher McGuigan、Paola Murziani、Magdalena Slusarczyk、Blanka Gonczy、Johan Vande Voorde、Sandra Liekens、Jan Balzarini

  DOI：10.1021/jm200815w

  日期：2011.10.27

  The fluorinated pyrimidine family of nucleosides continues to represent major current chemotherapeutic agents for treating solid tumors. We herein report their phosphate prodrugs, ProTides, as promising new derivatives, which partially bypass the dependence of the current drugs on active transport and nucleoside kinase-mediated activation. They are also resistant to metabolic deactivation by phosphorolytic enzymes. We report 39 ProTides of the fluorinated pyrimidine FUDR with variation in the aryl, ester, and amino acid. regions. Notably, only certain ProTide motifs are successful in delivering the nucleoside monophosphate into intact cells. We also find that the ProTides retain activity in mycoplasma infected cells, unlike FUDR. Data suggest these compounds to be worthy of further progression.