N¹-(2-furanidyl)-N³-(2-hydroxyethyl)-5-fluorouracil | 82178-07-2

• 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: N¹-(2-furanidyl)-N³-(2-hydroxyethyl)-5-fluorouracil
• 英文别名: N³-(2-hydroxyethyl) Tegafur；N¹-(2-furanidyl)-N³-(hydroxyethyl)-5-fluorouracil；5-Fluoro-3-(2-hydroxyethyl)-1-(oxolan-2-yl)pyrimidine-2,4-dione
• CAS: 82178-07-2
• 化学式: C₁₀H₁₃FN₂O₄
• 分子量: 244.223
• InChiKey: MMZQCAHRYVWFCI-UHFFFAOYSA-N

物化性质

• 沸点：
  371.0±52.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N¹-(2-furanidyl)-N³-(2-hydroxyethyl)-5-fluorouracil 在 二甲基亚砜 、 N,N'-二环己基碳二亚胺 、 草酸 作用下， 以 甲醇 为溶剂， 反应 1.67h， 生成 [5-Fluoro-2,6-dioxo-3-(tetrahydro-furan-2-yl)-3,6-dihydro-2H-pyrimidin-1-yl]-acetaldehyde
  参考文献：
  名称：

  α-羟基（硫代）膦酸酯的新型 N1-（2-呋喃基）-5-氟尿嘧啶衍生物的合成

  摘要：

  通过N1-(2-呋喃烷基)-N3-(羟烷基)-5-氟尿嘧啶的Moffatt法氧化，然后加入硫代亚磷酸二乙酯，合成了几种α-羟基硫代膦酸酯的N1-(2-呋喃基)-5-氟尿嘧啶衍生物. 通过用间氯过苯甲酸氧化相应的硫代膦酸盐获得膦酸盐产物。化合物6a的晶体结构由X射线衍射确定。© 2002 Wiley Periodicals, Inc. 杂原子化学 13:211–215, 2002; 在线发表于 Wiley Interscience (www.interscience.wiley.com)。DOI 10.1002/hc.10021

  DOI：

  10.1002/hc.10021
• 作为产物：
  描述：

  在 triethylamine tris(hydrogen fluoride) 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 N¹-(2-furanidyl)-N³-(2-hydroxyethyl)-5-fluorouracil
  参考文献：
  名称：

  含胸苷酸合酶抑制剂和代谢修饰剂的多作用铂（IV）前药，可对抗三阴性乳腺癌。

  摘要：

  多功能铂IV抗癌前药具有丰富的抗癌特性并克服铂II抗癌药耐药性和副作用的临床问题的潜力。在本文中，我们开发了具有针对性和生物活性功能的双重和三重作用的铂IV络合物。由顺铂，替加氟和lonidamine组成的一种复合物（PFL）对三阴性乳腺癌（TNBC）细胞表现出强大的细胞毒性。细胞摄取和分布研究表明，PFL主要聚集在线粒体中。结果，PFL破坏线粒体的超微结构并诱导线粒体膜电位发生重大变化，从而进一步导致MDA-MB-231 TNBCs中活性氧（ROS）的产生增加和ATP合成减少。蛋白质印迹分析揭示了胸苷酸合酶的三元复合物的形成，其表明替加福从PFL释放后胞内转化成5-FU 。此外，用PFL进行治疗会损害线粒体功能，从而抑制糖酵解和线粒体呼吸，并通过线粒体途径诱导细胞凋亡。RNA测序实验表明PFL会干扰DNA合成，DNA损伤，代谢和转录活性中涉及的途径。这些发现表明，PFL介入了几种细胞过程

  DOI：

  10.1021/acs.inorgchem.0c01736

文献信息

• SYNTHESIS OF SULFUR ANALOGUES OF CYCLIC PHOSPHOLIPID CONJUGATED WITH N¹-(2-FURANIDYL)-N³-(2-HYDROXYETHYL)-5-FLUOROURACIL
  作者：Chengxiang Zhang、Ruyu Chen、Chuchi Tang、Zhongbiao Zhang

  DOI：10.1080/10426509808036983

  日期：1998.1.1

  Abstract Two types of cyclic polythiophospholipid conjugated with N1 -(2-fu ran idyl)-N3-(2-hydroxyethyl)-5-fluorouracil were synthesized. The hexaethyl phosphorous triamide, activated by a catalytic amount of iodine, was used as the phosphorylating reagent in a one-pot reaction resulting in a number of novel phospholipid-drug conjugates.

  摘要 合成了两种与N1-(2-呋喃烷基)-N3-(2-羟乙基)-5-氟尿嘧啶结合的环状多硫代磷脂。由催化量的碘活化的六乙基磷三酰胺用作一锅反应中的磷酸化试剂，产生了许多新型磷脂-药物偶联物。
• Synthesis and cytotoxicity of novel fatty acid-nucleoside conjugates
  作者：Yun-Xiao Zhang、Gui-Fu Dai、Le Wang、Jing-Chao Tao

  DOI：10.1016/j.bmcl.2006.12.092

  日期：2007.3

  N3-Hydroxyethyltegafur (3) was synthesized in 91.0% yield under a new condition. A series of novel fatty acid esters of 3 were synthesized. These fatty acid-nucleoside conjugates have shown cytotoxicities against Ec9706 cells and A549 cells, and the structure activity relationship was discussed. (c) 2007 Elsevier Ltd. All rights reserved.
• SYNTHESIS OF PHOSPHOLIPID CONJUGATES OF N¹-(2-FURANIDYL)-N³-(2-HYDROXYETHYL)-5-FLUOROURACIL
  作者：Huanming Chen、Ruyu Chen、Pingying Li

  DOI：10.1080/10426509708043490

  日期：1997.3.1

  The synthesis of phospholipid conjugates of N-1-(2-furanidyl)-N-3-(2-hydroxyethyl)-5-fluorouracil is reported. The strategy for the synthesis is using hexaethylphosphorous triamide, activated by a catalytic amount of iodine, as the phosphorylating reagent in a one-pot reaction resulting in a number of new types of phospholipid-drug conjugates.
• Synthesis of Novel Phosphoramide-Tegafur Derivatives Containing Aminopropylsilatrane
  作者：De Qing Shi、Qi Chen、Zhong Hua Li、Xiao Peng Liu

  DOI：10.1080/104265090885039

  日期：2005.7.1

  A series of novel phosphoramide-tegafur derivatives containing gamma-aminopropyl silatrane were synthesized Via the condensation reactions of phosphoryl dichloride with N-1-(2-furanidyl)-N-3-(hydroxyethyl)-5-fluorouracil, followed by condensation with gamma-aminopropyl silatrane. The structures of the products were confirmed by H-1 NMR, P-31 NMR, IR, MS, and elemental analysis. The results of preliminary bioassay showed that the new compounds had an inhibition effect against HCT-8 and Bel-7402 cell lines.
• Synthesis of Novel Optically Active Cyclic Phospholipid Conjugates of Tegafur and Uridine Starting From L-Serine
  作者：Zheng-Jie He、Wen-Bin Chen、Cheng-Xiang Zhang、Zheng-Hong Zhou、Chu-Chi Tang

  DOI：10.1080/00397910008087103

  日期：2000.3

  Starting from L-serine, cyclic phospholids 2,3 and 4 were synthesized and successfully separated in the form of pure diastereomer. Their configurations were discussed and assigned according to their NMR spectra data. The asymmetric induction effects were also observed in two phosphorylation cyclizations.