5'-O-mesyl-2',3'-bis(benzyloxy)-5-fluorouridine | 113548-94-0

• 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'-O-mesyl-2',3'-bis(benzyloxy)-5-fluorouridine
• 英文别名: [(2R,3R,4R,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-bis(phenylmethoxy)oxolan-2-yl]methyl methanesulfonate
• CAS: 113548-94-0
• 化学式: C₂₄H₂₅FN₂O₈S
• 分子量: 520.536
• InChiKey: PGNJMLYAHCSFMP-YYTDSSBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.72
• 重原子数：
  36.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  125.92
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  5'-O-mesyl-2',3'-bis(benzyloxy)-5-fluorouridine 在 palladium dihydroxide potassium tert-butylate 、 氢气 、 氟化氢吡啶 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， -50.0~25.0 ℃ 、310.27 kPa 条件下， 反应 11.0h， 生成 5-氟-1-(5-氟-3,4-二羟基-5-甲基四氢呋喃-2-基)嘧啶-2,4-二酮
  参考文献：
  名称：

  Synthesis and interaction with uridine phosphorylase of 5'-deoxy-4',5-difluorouridine, a new prodrug of 5-fluorouracil

  摘要：

  5'-Deoxy-4',5-difluorouridine (4'-F-5'-dFUrd) (10) has been synthesized on the basis of the rationale that the labilization of the glycosidic linkage caused by the 4'-fluoro substituent might allow this compound to be a better prodrug form of the anticancer drug 5-fluorouracil (FUra) than is the widely studied fluoropyrimidine 5'-deoxy-5-fluorouridine (5'-dFUrd). The rate of solvolytic hydrolysis of the glycosidic linkage of 4'-F-5'-dFUrd at pH 1 was about 500-fold faster than that of 5'-dFUrd. Since uridine phosphorylase is thought to be the enzyme that causes degradation of 5'-dFUrd in vivo to generate FUra, we compared the substrate interactions of 5'-dFUrd and 4'-F-5'-dUrd with this enzyme. The Vmax for hydrolysis of 4'-F-5'-dFUrd to FUra by uridine phosphorylase was about 5-fold greater than that of 5'-dFUrd, whereas the Km value of 4'-F-5'-dFUrd was 10-fold lower. The combination of these two factors results in 4'-F-5'-dFUrd having a 50-fold higher value of V/K than does 5'-dFUrd. Against L1210 cells in culture, the IC50 value for growth inhibition by 4'-F-5'-dFUrd was 3 X 10(-7) compared to 3 X 10(-6) for 5'-dFUrd.

  DOI：

  10.1021/jm00401a008
• 作为产物：
  描述：

  2',3'-bis(benzyloxy)-5-fluorouridine 生成 5'-O-mesyl-2',3'-bis(benzyloxy)-5-fluorouridine
  参考文献：
  名称：

  AJMERA, SUDHIR;BAPAT, ASHOK R.;STEPHANIAN, EDIC;DANENBERG, PETER V., J. MED. CHEM., 31,(1988) N 6, 1094-1098

  摘要：

  DOI：