[N1-(5-chloropent-4-ene-2-yne-1-yl)-N3-(prop-2-yne-1-yl)]uracil | 450356-86-2

• 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-(5-chloropent-4-ene-2-yne-1-yl)-N3-(prop-2-yne-1-yl)]uracil
• CAS: 450356-86-2
• 化学式: C₁₂H₉ClN₂O₂
• 分子量: 248.669
• InChiKey: QHRPKQUIEQZGKC-DAXSKMNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.0
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [N1-(5-chloropent-4-ene-2-yne-1-yl)-N3-(prop-2-yne-1-yl)]uracil 在 四(三苯基膦)钯 、 正丁胺 作用下， 以 四氢呋喃 、 乙醇 、 溶剂黄146 为溶剂， 反应 72.5h， 生成 cis-1,2-di[3-(methoxycarbonylmethylthio)propyn-1-yl]ethene
  参考文献：
  名称：

  A Novel Approach towards Studying Non-Genotoxic Enediynes as Potential Anticancer Therapeutics

  摘要：

  A novel uracil-containing enediyne 7 was synthesized by the fusion at N-1 and N-3 of uracil with an 11-membered cyclic enediyne. Compound 7 was found to be stable against cycloaromatization at 80degreesC. Thus. it did not cause DNA-damage. Unlike other alkylated uracil derivatives 2-6, highly strained uracil-containing enediyne 7 was reacted with methyl thioglycolate at 25 degreesC to produce uracil (1) and linear enediyne 8. This reactivity toward a sulfhydryl group may play a significant role in the mechanism by which compound 7 directed its cytotoxicity toward tumor cell lines. Tumor cells were found to be more susceptible to enediyne 7 than normal human embryonic lung cells. A combination of 7 with adriamycin or 1-(beta-D-arabinofuranosyl)cytosine resulted in synergistic anticancer activity against murine L1210 and P388 leukemias, Sarcoma 180, and human CCRF-CEM lymphoblastic leukemia. After treatment of Molt-4 cells with uracil-containing enediyne 7. light microscope examination demonstrated the presence of cell shrinkage and nuclear segmentation. Treatment of cultured Molt-4 human leukemia cells with enediyne 7 resulted in a time-dependent depletion of glutathione (GSH) whereas the exposure of the cells to the GSH precursor N-acetylcysteine (NAC) resulted in a substantial suppression of this effect. As such, involvement of GSH depletion in the process of apoptosis may explain the mechanism of action of non-genotoxic enediyne 7 against malignant tumor cell lines. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00393-5
• 作为产物：
  描述：

  1-(丙-2-炔-1-基)嘧啶-2,4(1H,3H)-二酮 在 四(三苯基膦)钯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 正丁胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 22.5h， 生成 [N1-(5-chloropent-4-ene-2-yne-1-yl)-N3-(prop-2-yne-1-yl)]uracil
  参考文献：
  名称：

  A Novel Approach towards Studying Non-Genotoxic Enediynes as Potential Anticancer Therapeutics

  摘要：

  A novel uracil-containing enediyne 7 was synthesized by the fusion at N-1 and N-3 of uracil with an 11-membered cyclic enediyne. Compound 7 was found to be stable against cycloaromatization at 80degreesC. Thus. it did not cause DNA-damage. Unlike other alkylated uracil derivatives 2-6, highly strained uracil-containing enediyne 7 was reacted with methyl thioglycolate at 25 degreesC to produce uracil (1) and linear enediyne 8. This reactivity toward a sulfhydryl group may play a significant role in the mechanism by which compound 7 directed its cytotoxicity toward tumor cell lines. Tumor cells were found to be more susceptible to enediyne 7 than normal human embryonic lung cells. A combination of 7 with adriamycin or 1-(beta-D-arabinofuranosyl)cytosine resulted in synergistic anticancer activity against murine L1210 and P388 leukemias, Sarcoma 180, and human CCRF-CEM lymphoblastic leukemia. After treatment of Molt-4 cells with uracil-containing enediyne 7. light microscope examination demonstrated the presence of cell shrinkage and nuclear segmentation. Treatment of cultured Molt-4 human leukemia cells with enediyne 7 resulted in a time-dependent depletion of glutathione (GSH) whereas the exposure of the cells to the GSH precursor N-acetylcysteine (NAC) resulted in a substantial suppression of this effect. As such, involvement of GSH depletion in the process of apoptosis may explain the mechanism of action of non-genotoxic enediyne 7 against malignant tumor cell lines. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00393-5