1-(5-deoxy-4-fluoro-2,3-isopropylidene-α-L-lyxofuranosyl)-5-fluorouracil | 113548-92-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(5-deoxy-4-fluoro-2,3-isopropylidene-α-L-lyxofuranosyl)-5-fluorouracil
• 英文别名: 1-[(3aS,4R,6R,6aR)-4-fluoro-2,2,4-trimethyl-6,6a-dihydro-3aH-furo[3,4-d][1,3]dioxol-6-yl]-5-fluoropyrimidine-2,4-dione
• CAS: 113548-92-8
• 化学式: C₁₂H₁₄F₂N₂O₅
• 分子量: 304.25
• InChiKey: IEBDFHLJRQCSEF-GUKKNSHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(5-deoxy-2,3-O-isopropylidene-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85%的产率得到1-(5-deoxy-4-fluoro-2,3-isopropylidene-α-L-lyxofuranosyl)-5-fluorouracil
  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：——