N-(4-chloro-2,5-dimethoxyphenyl)-6-methoxy-7-(2-methoxyethoxy)quinazolin-4-amine | 872331-52-7

• 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: N-(4-chloro-2,5-dimethoxyphenyl)-6-methoxy-7-(2-methoxyethoxy)quinazolin-4-amine
• CAS: 872331-52-7
• 化学式: C₂₀H₂₂ClN₃O₅
• 分子量: 419.865
• InChiKey: QDFDIBXGAVZBLX-UHFFFAOYSA-N

物化性质

• 熔点：
  214-217 °C
• 沸点：
  544.7±50.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  84
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(4-chloro-2,5-dimethoxyphenyl)-6-methoxy-7-(2-methoxyethoxy)quinazolin-4-amine 在 ammonium cerium(IV) nitrate 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 1.0h， 以69%的产率得到2-氯-5-(6-甲氧基-7-(2-甲氧基乙氧基)喹唑啉-4-氨基)-2,5-环己二烯-1,4-二酮
  参考文献：
  名称：

  2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as Covalent-Binding, Irreversible Inhibitors of the Kinase Domain of Vascular Endothelial Growth Factor Receptor-2

  摘要：

  A series of 2-(quinazolin-4-ylamino)-[1,4] benzoquinone derivatives that function as potent covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2 (VEGFR-2) has been prepared by ceric ammonium nitrate oxidation of substituted (2,5-dimethoxyphenyl)(6,7-disubstituted-quinazolin-4-yl)amines and by displacement of the chlorine atom of substituted 2-chloro-5-(6,7-disubstituted-quinazolin-4-ylamino)-[1,41benzoquinones with various amines, anilines, phenols, and alcohols. Enzyme studies were conducted in the absence and presence of glutathione and plasma. Several of the compounds inhibit VEGF-stimulated autophosphorylation in intact cells. Kinetic experiments were performed to study the reactivity of selected inhibitors toward glutathione. Reactivities correlated with LUMO energies calculated as averages of those of individual conformers weighted by the Boltzmann distribution. These results and molecular modeling were used to rationalize the biological observations. The compounds behave as non-ATP-competitive inhibitors. Unequivocal evidence, from mass spectral studies, indicates that these inhibitors form a covalent interaction with Cys-1045. One member of this series displays antitumor activity in an in vivo model.

  DOI：

  10.1021/jm050559f
• 作为产物：
  描述：

  4-羟基-3-甲氧基苯甲腈 在 palladium on activated charcoal 硝酸铵 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸酐 、 环己烯 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 N-(4-chloro-2,5-dimethoxyphenyl)-6-methoxy-7-(2-methoxyethoxy)quinazolin-4-amine
  参考文献：
  名称：

  2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as Covalent-Binding, Irreversible Inhibitors of the Kinase Domain of Vascular Endothelial Growth Factor Receptor-2

  摘要：

  A series of 2-(quinazolin-4-ylamino)-[1,4] benzoquinone derivatives that function as potent covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2 (VEGFR-2) has been prepared by ceric ammonium nitrate oxidation of substituted (2,5-dimethoxyphenyl)(6,7-disubstituted-quinazolin-4-yl)amines and by displacement of the chlorine atom of substituted 2-chloro-5-(6,7-disubstituted-quinazolin-4-ylamino)-[1,41benzoquinones with various amines, anilines, phenols, and alcohols. Enzyme studies were conducted in the absence and presence of glutathione and plasma. Several of the compounds inhibit VEGF-stimulated autophosphorylation in intact cells. Kinetic experiments were performed to study the reactivity of selected inhibitors toward glutathione. Reactivities correlated with LUMO energies calculated as averages of those of individual conformers weighted by the Boltzmann distribution. These results and molecular modeling were used to rationalize the biological observations. The compounds behave as non-ATP-competitive inhibitors. Unequivocal evidence, from mass spectral studies, indicates that these inhibitors form a covalent interaction with Cys-1045. One member of this series displays antitumor activity in an in vivo model.

  DOI：

  10.1021/jm050559f