5'-(2'-deoxy-2',2'-difluorocytidyl) 5-nitrofurfuryl N-methyl-N-(4-chlorobutyl)phosphoramidate

• 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'-(2'-deoxy-2',2'-difluorocytidyl) 5-nitrofurfuryl N-methyl-N-(4-chlorobutyl)phosphoramidate
• 英文别名: 4-amino-1-[(2R,4R,5R)-5-[[[4-chlorobutyl(methyl)amino]-[(5-nitrofuran-2-yl)methoxy]phosphoryl]oxymethyl]-3,3-difluoro-4-hydroxyoxolan-2-yl]pyrimidin-2-one
• 化学式: C₁₉H₂₅ClF₂N₅O₉P
• 分子量: 571.859
• InChiKey: VYOGFXOEPZYEJF-JYRSQUOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  186
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  盐酸吉西他滨 在 四(三苯基膦)钯 吡啶 、 N-甲基咪唑 、 4-二甲氨基吡啶 、 ammonium sulfate 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 27.0h， 生成 5'-(2'-deoxy-2',2'-difluorocytidyl) 5-nitrofurfuryl N-methyl-N-(4-chlorobutyl)phosphoramidate
  参考文献：
  名称：

  Synthesis and Biological Activity of a Gemcitabine Phosphoramidate Prodrug

  摘要：

  A gemcitabine (2',2'-difluorodeoxycytidine, dFdC) phosphoramidate prodrug designed for the intracellular delivery of gemcitabine 5'-monophosphate was synthesized. The prodrug was about an order of magnitude less active than gemcitabine against wild-type cells, and the nucleoside transport inhibitor dipyridamole reduced prodrug activity. The prodrug was more active than gemcitabine against two deoxycytidine kinase-deficient cell lines. The results suggest that the prodrug is a potent growth inhibitor that can bypass dCK deficiency at higher drug concentrations.

  DOI：

  10.1021/jm070269u

文献信息

• Synthesis and Biological Activity of a Gemcitabine Phosphoramidate Prodrug
  作者：Weidong Wu、Jennifer Sigmond、Godefridus J. Peters、Richard F. Borch

  DOI：10.1021/jm070269u

  日期：2007.7.1

  A gemcitabine (2',2'-difluorodeoxycytidine, dFdC) phosphoramidate prodrug designed for the intracellular delivery of gemcitabine 5'-monophosphate was synthesized. The prodrug was about an order of magnitude less active than gemcitabine against wild-type cells, and the nucleoside transport inhibitor dipyridamole reduced prodrug activity. The prodrug was more active than gemcitabine against two deoxycytidine kinase-deficient cell lines. The results suggest that the prodrug is a potent growth inhibitor that can bypass dCK deficiency at higher drug concentrations.