bis(pivaloyloxymethyl) 8-aza-2'-deoxyadenosine-5'-monophosphate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: bis(pivaloyloxymethyl) 8-aza-2'-deoxyadenosine-5'-monophosphate
• 英文别名: [[(2R,3S,5R)-5-(7-aminotriazolo[4,5-d]pyrimidin-3-yl)-3-hydroxyoxolan-2-yl]methoxy-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
• 化学式: C₂₁H₃₃N₆O₁₀P
• 分子量: 560.501
• InChiKey: GLRVVZZKJZPIAN-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  209
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  7-amino-3-<2'-deoxy-3',5'-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl>-3H-1,2,3-triazolo<4,5-d>pyrimidine 在 磷酸三甲酯 、 氨 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 77.75h， 生成 bis(pivaloyloxymethyl) 8-aza-2'-deoxyadenosine-5'-monophosphate
  参考文献：
  名称：

  Enhancement of Nucleoside Cytotoxicity through Nucleotide Prodrugs

  摘要：

  A common reason for the lack of cytotoxicity of certain nucleosides is thought to be their inability to be initially activated to the monophosphate level by a nucleoside kinase or other activating enzyme. In a search for other nucleosides that might be worthwhile anticancer agents, we have begun to examine the utilization of monophosphate prodrugs in order to explore whether any enhanced cytotoxicity might be found for the prodrugs of candidate nucleosides that have little or no cytotoxicity. To that end, 5'-bis(pivaloyloxymethyl) phosphate prodrugs of two weakly cytotoxic compounds, 8-aza-2'-deoxyadenosine (5) and 8-bromo-2'-deoxyadenosine (9), have been prepared. These prodrugs (8 and 12) were examined for their cytotoxicity in CEM cells and were found to possess significantly enhanced cytotoxicity when compared with the corresponding parent nucleosides. Further cell culture experiments were conducted to gain insight into the mechanisms of cytotoxicity of these two prodrugs, and those data are reported.

  DOI：

  10.1021/jm020107s

文献信息

• Enhancement of Nucleoside Cytotoxicity through Nucleotide Prodrugs
  作者：Jerry D. Rose、William B. Parker、Hitoshi Someya、Sue C. Shaddix、John A. Montgomery、John A. Secrist

  DOI：10.1021/jm020107s

  日期：2002.9.1

  A common reason for the lack of cytotoxicity of certain nucleosides is thought to be their inability to be initially activated to the monophosphate level by a nucleoside kinase or other activating enzyme. In a search for other nucleosides that might be worthwhile anticancer agents, we have begun to examine the utilization of monophosphate prodrugs in order to explore whether any enhanced cytotoxicity might be found for the prodrugs of candidate nucleosides that have little or no cytotoxicity. To that end, 5'-bis(pivaloyloxymethyl) phosphate prodrugs of two weakly cytotoxic compounds, 8-aza-2'-deoxyadenosine (5) and 8-bromo-2'-deoxyadenosine (9), have been prepared. These prodrugs (8 and 12) were examined for their cytotoxicity in CEM cells and were found to possess significantly enhanced cytotoxicity when compared with the corresponding parent nucleosides. Further cell culture experiments were conducted to gain insight into the mechanisms of cytotoxicity of these two prodrugs, and those data are reported.