1-naphthyl(ethoxydimethylglycinyl)phosphorochloridate | 1092106-41-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-naphthyl(ethoxydimethylglycinyl)phosphorochloridate
• 英文别名: naphthyl(ethoxydimethylglycinyl)phosphochloridate
• CAS: 1092106-41-6
• 化学式: C₁₆H₁₉ClNO₄P
• 分子量: 355.758
• InChiKey: COBYIFKNDZFYCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-naphthyl(ethoxydimethylglycinyl)phosphorochloridate 、 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2%的产率得到5-fluoro-2'-deoxyuridine-5'-O-[1-naphthyl(ethoxy-α,α-dimethylglycine)]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
• 作为产物：
  描述：

  1-萘基二氯磷酸酯 、 2-氨基异丁酸乙酯盐酸盐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-naphthyl(ethoxydimethylglycinyl)phosphorochloridate
  参考文献：
  名称：

  Activation of p16 Gene Silenced by DNA Methylation in Cancer Cells by Phosphoramidate Derivatives of 2′-Deoxyzebularine

  摘要：

  We report herein the application of the phosphoramidate ProTide technology to improve the metabolism of the DNA methytransferase inhibitor, zebularine (Z). Zebularine is a riboside that must undergo a complex metabolic transformation before reaching the critical 2'-deoxyzebularine 5'-triphosphate (dZTP). Because 2'-deoxyzebularine (dZ) is not phosphorylated and therefore inactive, the ProTide strategy was employed to bypass the lack of phosphorylation of dZ and the inefficient reduction of zebularine 5'-diphosphate by ribonucleotide-diphosphate reductase required for zebularine. Several compounds were identified as more potent inhibitors of DNA methylation and stronger inducers of p16 tumor suppressor gene than zebularine. However, their activity was dependent on the administration of thymidine to overcome the potent inhibition of thymidylate synthase (TS) and deoxycytidine monophosphate (dCMP) deaminase by dZMP, which deprives cells of essential levels of thymidine. Intriguingly, the activity of the ProTides was cell line-dependent, and activation of p16 was manifest only in Cf-Pac-1 pancreatic ductal adenocarcinoma. cells.

  DOI：

  10.1021/jm8005965