1,5-anhydro-2,3-dideoxy-2-(5-fluorouracil-1-yl)-D-arabino-hexitol | 161263-52-1

• 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-anhydro-2,3-dideoxy-2-(5-fluorouracil-1-yl)-D-arabino-hexitol
• 英文别名: 5-fluoro-1-[(3S,5S,6R)-5-hydroxy-6-(hydroxymethyl)oxan-3-yl]pyrimidine-2,4-dione
• CAS: 161263-52-1
• 化学式: C₁₀H₁₃FN₂O₅
• 分子量: 260.222
• InChiKey: MMJSIZUWZSBJLM-APQOSEDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,5-anhydro-2,3-dideoxy-2-(5-fluorouracil-1-yl)-D-arabino-hexitol 在 吡啶 、 ammonium hydroxide 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 78.0h， 生成 Acetic acid (2R,3S,5S)-2-acetoxymethyl-5-(4-amino-5-fluoro-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-pyran-3-yl ester
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Structure Analysis of a Series of New 1,5-Anhydrohexitol Nucleosides

  摘要：

  In view of the selective anti-HSV activity of 1,5-anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol,(1) a series of novel 1,5-anhydrohexitol nucleosides were synthesized and evaluated for their inhibitory activity against several viruses. The 5-iodouracil 3 and the 5-ethyluracil 4 derivatives are highly selective TK-dependent inhibitors of HSV-1 and HSV-2. Broad anti-herpes virus activity was noticed for 5-fluorocytosine 6 and 2,6-diaminopurine 10 analogues. From a transport study of 3, using the thymidine influx competition method, one can conclude that intracellular uptake of this compound most probably occurs by passive diffusion. X-ray analysis of compounds 3 and 9 showed that the heterocyclic base of 1,5-anhydrohexitol pyrimidine and purine is placed in the axial position and that the sugar ring adopts a slightly distorted chair conformation.

  DOI：

  10.1021/jm00005a010
• 作为产物：
  描述：

  1,5-脱水-3-脱氧-4,6-O-(苯基亚甲基)-D-核-己糖醇 在 氨 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 生成 1,5-anhydro-2,3-dideoxy-2-(5-fluorouracil-1-yl)-D-arabino-hexitol
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Structure Analysis of a Series of New 1,5-Anhydrohexitol Nucleosides

  摘要：

  In view of the selective anti-HSV activity of 1,5-anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol,(1) a series of novel 1,5-anhydrohexitol nucleosides were synthesized and evaluated for their inhibitory activity against several viruses. The 5-iodouracil 3 and the 5-ethyluracil 4 derivatives are highly selective TK-dependent inhibitors of HSV-1 and HSV-2. Broad anti-herpes virus activity was noticed for 5-fluorocytosine 6 and 2,6-diaminopurine 10 analogues. From a transport study of 3, using the thymidine influx competition method, one can conclude that intracellular uptake of this compound most probably occurs by passive diffusion. X-ray analysis of compounds 3 and 9 showed that the heterocyclic base of 1,5-anhydrohexitol pyrimidine and purine is placed in the axial position and that the sugar ring adopts a slightly distorted chair conformation.

  DOI：

  10.1021/jm00005a010

文献信息

• Synthesis, Biological Evaluation, and Structure Analysis of a Series of New 1,5-Anhydrohexitol Nucleosides
  作者：Ilse Verheggen、Arthur Van Aerschot、Luc Van Meervelt、Jef Rozenski、Leonard Wiebe、Robert Snoeck、Graciela Andrei、Jan Balzarini、Paul Claes

  DOI：10.1021/jm00005a010

  日期：1995.3

  In view of the selective anti-HSV activity of 1,5-anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol,(1) a series of novel 1,5-anhydrohexitol nucleosides were synthesized and evaluated for their inhibitory activity against several viruses. The 5-iodouracil 3 and the 5-ethyluracil 4 derivatives are highly selective TK-dependent inhibitors of HSV-1 and HSV-2. Broad anti-herpes virus activity was noticed for 5-fluorocytosine 6 and 2,6-diaminopurine 10 analogues. From a transport study of 3, using the thymidine influx competition method, one can conclude that intracellular uptake of this compound most probably occurs by passive diffusion. X-ray analysis of compounds 3 and 9 showed that the heterocyclic base of 1,5-anhydrohexitol pyrimidine and purine is placed in the axial position and that the sugar ring adopts a slightly distorted chair conformation.