phthalazonyl glycol ether | 69776-14-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: phthalazonyl glycol ether
• 英文别名: 1(2H)-Phthalazonyl-4-(2-hydroxyethyl)-ether；4-(2-hydroxy-ethoxy)-2H-phthalazin-1-one；4-(2-hydroxyethoxy)-2H-phthalazin-1-one
• CAS: 69776-14-3
• 化学式: C₁₀H₁₀N₂O₃
• 分子量: 206.201
• InChiKey: VFDSNWCRVWJTQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  70.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  iodoferrocene 、 phthalazonyl glycol ether 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 potassium carbonate 作用下， 以 三乙胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以26%的产率得到2-ferrocenyl-4-(2-hydroxyethoxy)phthalazin-1(2H)-one
  参考文献：
  名称：

  N -ferrocenylpyridazinones and new organic analogues: Synthesis, cyclic voltammetry, DFT analysis and in vitro antiproliferative activity associated with ROS-generation

  摘要：

  Employing an optimized Pd-catalyzed cross-coupling reaction promoted by CuI, novel N-ferrocenylpyridazinones along with N-phenyl- and N-(2-pyridyl) analogues were synthesized from readily available heterocyclic precursors, iodoferrocene, iodobenzene and 2-bromopyridine. With exception of the ferrocenylation of 6-ferrocenylpyridazin-3(2H)-one yielding both N- and O-substituted products, the studied reactions exclusively afforded N-aryl lactams. The novel compounds exhibited cytotoxicity towards HEPG2 and HT-29 human malignant cells under in vitro conditions. The measured IC50 values supplemented with the results of cyclic voltammetry and DFT calculations suggest that the cytotoxic activity of the N- and O-ferrocenyl-substituted derivatives and the decreased effect of the N-phenyl analogues seem to be at least partly associated with the potential to generate reactive oxygen species (ROS). This interpretation, allowing the prediction of characteristic substituent-dependent SAR, was supported by the results of related studies on the practically inactive N-(2-pyridyl)pyridazinones assumed to be present in protonated chelate forms with highly a decreased propensity to undergo ionization. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2017.09.015
• 作为产物：
  描述：

  4-[(2-羟基乙基)氨基]-1(2H)-酞嗪酮 在 盐酸 、 硫酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 20.0h， 生成 phthalazonyl glycol ether
  参考文献：
  名称：

  Koermendy, K.; Ruff, F., Acta Chimica Hungarica, 1983, vol. 112, # 1, p. 65 - 82

  摘要：

  DOI：

文献信息

• Koermendy, K.; Ruff, F., Acta Chimica Academiae Scientiarum Hungaricae, 1981, vol. 106, # 2, p. 155 - 166
  作者：Koermendy, K.、Ruff, F.

  DOI：——

  日期：——
• KOERMENDY K.; RUFF F., ACTA CHIM. ACAD. SCI. HUNG., 1981, 106, NO 2, 155-166
  作者：KOERMENDY K.、 RUFF F.

  DOI：——

  日期：——
• KOERMENDY, K.;RUFF, F., ACTA CHIM. HUNG., 1983, 112, N 1, 65-81
  作者：KOERMENDY, K.、RUFF, F.

  DOI：——

  日期：——
• KOERMENDY K., ACTA CHIM. ACAD. SCI. HUNG., 1978, 98, NO 3, 303-313
  作者：KOERMENDY K.

  DOI：——

  日期：——
• N -ferrocenylpyridazinones and new organic analogues: Synthesis, cyclic voltammetry, DFT analysis and in vitro antiproliferative activity associated with ROS-generation
  作者：Tamás Jernei、Szilvia Bősze、Rita Szabó、Ferenc Hudecz、Katalin Majrik、Antal Csámpai

  DOI：10.1016/j.tet.2017.09.015

  日期：2017.10

  Employing an optimized Pd-catalyzed cross-coupling reaction promoted by CuI, novel N-ferrocenylpyridazinones along with N-phenyl- and N-(2-pyridyl) analogues were synthesized from readily available heterocyclic precursors, iodoferrocene, iodobenzene and 2-bromopyridine. With exception of the ferrocenylation of 6-ferrocenylpyridazin-3(2H)-one yielding both N- and O-substituted products, the studied reactions exclusively afforded N-aryl lactams. The novel compounds exhibited cytotoxicity towards HEPG2 and HT-29 human malignant cells under in vitro conditions. The measured IC50 values supplemented with the results of cyclic voltammetry and DFT calculations suggest that the cytotoxic activity of the N- and O-ferrocenyl-substituted derivatives and the decreased effect of the N-phenyl analogues seem to be at least partly associated with the potential to generate reactive oxygen species (ROS). This interpretation, allowing the prediction of characteristic substituent-dependent SAR, was supported by the results of related studies on the practically inactive N-(2-pyridyl)pyridazinones assumed to be present in protonated chelate forms with highly a decreased propensity to undergo ionization. (C) 2017 Elsevier Ltd. All rights reserved.