uridine 3'-(4-hydroxytamoxifen phosphate) | 1361392-98-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核糖核苷3'-磷酸盐
• 英文名称: uridine 3'-(4-hydroxytamoxifen phosphate)
• CAS: 1361392-98-4
• 化学式: C₃₅H₄₀N₃O₁₀P
• 分子量: 693.69
• InChiKey: ZIMRQKAMSCEBRO-HHAIGBBTSA-N

物化性质

• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.66
• 重原子数：
  49.0
• 可旋转键数：
  14.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  172.78
• 氢给体数：
  4.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  uridine 3'-(4-hydroxytamoxifen phosphate) 在 sodium chloride 作用下， 生成 阿非昔芬
  参考文献：
  名称：

  Ribonuclease-Activated Cancer Prodrug

  摘要：

  Cancer chemotherapeutic agents often have a narrow therapeutic index that challenges the maintenance of a safe and effective dose. Consistent plasma concentrations of a drug can be obtained by using a timed-release prodrug strategy. We reasoned that a ribonucleoside 3'-phosphate could serve as a pro-moiety that also increases the hydrophilicity of a cancer chemotherapeutic agent. Herein, we report an efficient route for the synthesis of the prodrug uridine 3'-(4-hydroxytamoxifen phosphate) (UpHT). UpHT demonstrates timed-released activation kinetics with a half-life of approximately 4 h at the approximate plasma concentration of human pancreatic ribonuclease (RNase 1). MCF-7 breast cancer cells treated with UpHT showed decreased proliferation upon coincubation with RNase 1, consistent with the release of the active drug-4-hydroxytamoxifen. These data demonstrate the utility of a human plasma enzyme as a useful activator of a prodrug.

  DOI：

  10.1021/ml2002554