diethyl cis-5-[N-(2-dimethylamino)ethylnaphthalimide-3-ylcarbamoyl]-2-methylisoxazolidin-3-yl-3-phosphonate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: diethyl cis-5-[N-(2-dimethylamino)ethylnaphthalimide-3-ylcarbamoyl]-2-methylisoxazolidin-3-yl-3-phosphonate
• 英文别名: (3R,5R)-3-diethoxyphosphoryl-N-[2-[2-(dimethylamino)ethyl]-1,3-dioxobenzo[de]isoquinolin-5-yl]-2-methyl-1,2-oxazolidine-5-carboxamide
• 化学式: C₂₅H₃₃N₄O₇P
• 分子量: 532.533
• InChiKey: DCLGLOOBQZOHBR-NHCUHLMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  氨萘非特 在 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 24.0h， 生成 diethyl cis-5-[N-(2-dimethylamino)ethylnaphthalimide-3-ylcarbamoyl]-2-methylisoxazolidin-3-yl-3-phosphonate 、 diethyl trans-5-[N-(2-dimethylamino)ethylnaphthalimide-3-ylcarbamoyl]-2-methylisoxazolidin-3-yl-3-phosphonate
  参考文献：
  名称：

  Design, antiviral and cytostatic properties of isoxazolidine-containing amonafide analogues

  摘要：

  A novel series of 5-arylcarbamoyl-and 5-arylmethyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesized via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-substituted naphthalimide acrylamides and N-allylnaphthalimides. All cis- and trans-isoxazolidine phosphonates obtained herein were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-9d and trans-9f exhibited the highest activity (EC50 = 8.9 mu M) toward cytomegalovirus. Compounds cis-and trans-9d as well as cis- and trans-9f were found potent against HSV and Vaccinia viruses (EC50 in the 45-58 mu M range), whereas isoxazolidines 10a and 10d suppressed replication of Coxsackie B4 and Punta Toro viruses (EC(5)0 in the 45-73 mu M range). Antiproliferative evaluation of all obtained isoxazolidines revealed the promising activity of cis-9b, cis-9d, trans-9d, cis-9e, trans-9e, cis-9f and trans-9f toward tested cancer cell lines with IC50 in the 1.1-19 mu M range. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.079

文献信息

• Design, antiviral and cytostatic properties of isoxazolidine-containing amonafide analogues
  作者：Kamil Kokosza、Graciela Andrei、Dominique Schols、Robert Snoeck、Dorota G. Piotrowska

  DOI：10.1016/j.bmc.2015.04.079

  日期：2015.7

  A novel series of 5-arylcarbamoyl-and 5-arylmethyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesized via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-substituted naphthalimide acrylamides and N-allylnaphthalimides. All cis- and trans-isoxazolidine phosphonates obtained herein were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-9d and trans-9f exhibited the highest activity (EC50 = 8.9 mu M) toward cytomegalovirus. Compounds cis-and trans-9d as well as cis- and trans-9f were found potent against HSV and Vaccinia viruses (EC50 in the 45-58 mu M range), whereas isoxazolidines 10a and 10d suppressed replication of Coxsackie B4 and Punta Toro viruses (EC(5)0 in the 45-73 mu M range). Antiproliferative evaluation of all obtained isoxazolidines revealed the promising activity of cis-9b, cis-9d, trans-9d, cis-9e, trans-9e, cis-9f and trans-9f toward tested cancer cell lines with IC50 in the 1.1-19 mu M range. (C) 2015 Elsevier Ltd. All rights reserved.