1,5-bis[5-fluoro-1-(β-2'-deoxyribofuranosyl)-2,4-dioxopyrimidinyl]-2,4-dimethylpropanone | 1395918-62-3

• 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: 1,5-bis[5-fluoro-1-(β-2'-deoxyribofuranosyl)-2,4-dioxopyrimidinyl]-2,4-dimethylpropanone
• 英文别名: FdUrd₂ B；5-fluoro-3-[4-[5-fluoro-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,6-dioxopyrimidin-1-yl]-3-oxopentan-2-yl]-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 1395918-62-3
• 化学式: C₂₃H₂₈F₂N₄O₁₁
• 分子量: 574.492
• InChiKey: IKVVLRDSXQWEJF-KZRMHPHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  198
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  1,3-bis[5-fluoro-1-(β-2'-deoxy-3',5'-di-O-acetylribofuranosyl)-2,4-dioxopyrimidinyl]-1,3-dimethylpropan-2-one 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 以87%的产率得到1,5-bis[5-fluoro-1-(β-2'-deoxyribofuranosyl)-2,4-dioxopyrimidinyl]-2,4-dimethylpropanone
  参考文献：
  名称：

  Synthesis and one-electron reduction characteristics of radiation-activated prodrugs possessing two 5-fluorodeoxyuridine units

  摘要：

  Two molecules of an antitumor agent, 5-fluorodeoxyuridine (5-FdUrd), were connected by a 2-oxoalkyl linker (Oxo-linker) at the N(3) position to obtain radiation-activated prodrugs, FdUrd(2) A and FdUrd(2) B. The prodrugs in this study released 5-FdUrd via one-electron reduction initiated by hypoxic X-irradiation. The release of 5-FdUrd from FdUrd(2) A and FdUrd(2) B proceeded more efficiently than that of previous prodrug, Oxo-FdUrd, which possessed one molecule of 5-FdUrd. FdUrd(2) A exhibited increased cytotoxicity against A549 cells when the FdUrd(2) A solution had been irradiated with a large dose of X-rays before administration to the cells. However, we observed no effect on cytotoxicity when the cells were X-irradiated under hypoxic conditions in the presence of FdUrd(2) A because the amount of 5-FdUrd released in the cells seemed to be too low to induce cytotoxic activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.008

文献信息

• Synthesis and one-electron reduction characteristics of radiation-activated prodrugs possessing two 5-fluorodeoxyuridine units
  作者：Kazuhito Tanabe、Masaaki Sugiura、Takeo Ito、Sei-ichi Nishimoto

  DOI：10.1016/j.bmc.2012.07.008

  日期：2012.9

  Two molecules of an antitumor agent, 5-fluorodeoxyuridine (5-FdUrd), were connected by a 2-oxoalkyl linker (Oxo-linker) at the N(3) position to obtain radiation-activated prodrugs, FdUrd(2) A and FdUrd(2) B. The prodrugs in this study released 5-FdUrd via one-electron reduction initiated by hypoxic X-irradiation. The release of 5-FdUrd from FdUrd(2) A and FdUrd(2) B proceeded more efficiently than that of previous prodrug, Oxo-FdUrd, which possessed one molecule of 5-FdUrd. FdUrd(2) A exhibited increased cytotoxicity against A549 cells when the FdUrd(2) A solution had been irradiated with a large dose of X-rays before administration to the cells. However, we observed no effect on cytotoxicity when the cells were X-irradiated under hypoxic conditions in the presence of FdUrd(2) A because the amount of 5-FdUrd released in the cells seemed to be too low to induce cytotoxic activity. (C) 2012 Elsevier Ltd. All rights reserved.