5'-deoxy-4',5-difluoro-2',3'-bis(benzyloxy)uridine | 113548-96-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5'-deoxy-4',5-difluoro-2',3'-bis(benzyloxy)uridine
• 英文别名: 5-fluoro-1-[(2R,3R,4S,5S)-5-fluoro-5-methyl-3,4-bis(phenylmethoxy)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 113548-96-2
• 化学式: C₂₃H₂₂F₂N₂O₅
• 分子量: 444.435
• InChiKey: HSHWVRLZVYAMAJ-MHXAIHSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.06
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  82.55
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  5'-deoxy-4',5-difluoro-2',3'-bis(benzyloxy)uridine 在 palladium dihydroxide 氢气 作用下， 以 1,4-二氧六环 为溶剂， 反应 10.0h， 以31%的产率得到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：

  1-(5-deoxy-2,3-bis(benzyloxy)-β-D-erythro-pent-4-enofuranosyl)-5-fluorouracil 在 氟化氢吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以86%的产率得到5'-deoxy-4',5-difluoro-2',3'-bis(benzyloxy)uridine
  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

文献信息

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

  DOI：——

  日期：——