bis(pivaloyloxymethyl)thymidine 5'-phosphate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: bis(pivaloyloxymethyl)thymidine 5'-phosphate
• 英文别名: [2,2-dimethylpropanoyloxymethoxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl]oxymethyl 2,2-dimethylpropanoate
• 化学式: C₂₂H₃₅N₂O₁₂P
• 分子量: 550.5
• InChiKey: GPVAVPSUOXLMJD-ARFHVFGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  176
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  ((hydroxyphosphoryl)bis(oxy))bis(methylene) bis(2,2-dimethylpropanoate) 、 beta-胸苷 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 120.0h， 以30%的产率得到bis(pivaloyloxymethyl)thymidine 5'-phosphate
  参考文献：
  名称：

  Bis(pivaloyloxymethyl) thymidine 5′-phosphate is a cell membrane-permeable precursor of thymidine 5′-phosphate in thymidine kinase deficient CCRF CEM cells

  摘要：

  Bis(pivaloyloxymethyl) thymidine 5-phosphate (POM2-dTMP) has been investigated as a membrane-permeable prodrugs of dTMP. The growth inhibitory activity of POM2-TMP has been compared with thymidine (TdR) in wild type CCRF CEM cells (CEM) and a strain that lacks TdR kinase (CEM tk-). After 72 h incubation at 37 degrees C, TdR showed significant antiproliferative activity (IC50 = 27 mu M) against CEM cells but was weakly effective (IC50 = 730 mu M) against the mutant cell line. By comparison, bis(pivaloyloxymethyl) thymidine 5'-monophosphate (POM2-dTMP) was equally inhibitory (IC50 = 5 mu M) to both cell lines. The growth inhibitory effects were reversed by deoxycytidine. Cellular [methyl-H-3]dTTP pools increased linearly over 2 h during incubation of CEM or CEM tk- with 5 mu M POM2-[methyl-H-3]dTMP. The incorporation of [methyl-H-3]TdR into HClO4-insoluble cell residue by CEM tk-was < 0.1% that of CEM and did not increase over I h. In contrast, CEM tk- incorporated radioactivity from POM2-dTMP into acid insoluble residue at a rate 59% that of CEM. These results demonstrate that POM2-dTMP can penetrate into cells and serve as a source of dTMP. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2005.02.008