5-methoxy-4-(2-methoxyethoxy)-2-nitrobenzonitrile | 870959-50-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-methoxy-4-(2-methoxyethoxy)-2-nitrobenzonitrile
• CAS: 870959-50-5
• 化学式: C₁₁H₁₂N₂O₅
• 分子量: 252.227
• InChiKey: CZYKWQHUTLXWEX-UHFFFAOYSA-N

物化性质

• 沸点：
  428.2±45.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-methoxy-4-(2-methoxyethoxy)-2-nitrobenzonitrile 在 palladium on activated charcoal ammonium cerium(IV) nitrate 、 溶剂黄146 、 环己烯 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 11.5h， 生成 2-chloro-3-methoxy-5-{[6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino}benzo-1,4-quinone
  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 硝酸铵 、 potassium carbonate 、 三氟乙酸酐 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 5-methoxy-4-(2-methoxyethoxy)-2-nitrobenzonitrile
  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

文献信息

• Bis-Quinazoline Derivatives as Inhibitors for Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase
  申请人：TETRANOV INTERNATIONAL, INC

  公开号：US20130296348A1

  公开（公告）日：2013-11-07

  Novel bis-quinazoline derivatives as tyrosine kinase inhibitors, synthesis of these compounds, and novel methods for treating tyrosine kinase mediated diseases or disorders using these compounds are disclosed. In particular, the present invention provides tethered quinazoline derivative dimers as inhibitors to the epidermal growth factor receptor (EGFR) tyrosine kinase, pharmaceutical compositions thereof, and their therapeutic uses for treating EGFR kinase-mediated diseases or disorders, such as various cancers, as well as synthetic methods for preparing these novel compounds.

  小说双嘧啶衍生物作为酪氨酸激酶抑制剂，揭示了这些化合物的合成方法，以及利用这些化合物治疗酪氨酸激酶介导的疾病或障碍的新方法。具体地，本发明提供了作为表皮生长因子受体（EGFR）酪氨酸激酶抑制剂的连接嘧啶衍生物二聚体，以及它们的药物组成部分，以及它们用于治疗EGFR激酶介导的疾病或障碍（如各种癌症）的治疗用途，以及用于制备这些新化合物的合成方法。
• Quinone Substituted Quinazoline and Quinoline Kinase Inhibitors
  申请人：Floyd Jr Brawner Middleton

  公开号：US20070299092A1

  公开（公告）日：2007-12-27

  The present invention provides for compounds with the general formula: A compound of formula (1) having the structure (1) wherein Z is a radical selected from the group (a), (b), or (c) as well as methods and compositions containing these compounds useful for treatment of diseases that are characterized, at least in part, by excessive, abnormal, or inappropriate angiogenesis. These disease states, include but are not limited to, cancer, diabetic retinopathy, macular degeneration and rheumatoid arthritis. These compounds inhibit angiogenesis by inhibiting a tyrosine kinase receptor enzyme, specifically KDR, and binding to the KDR in an irreversible manner.

  本发明提供了一般式为：具有结构式（1）的化合物，其中Z是从（a）、（b）或（c）组中选择的基团，以及包含这些化合物的方法和组合物，用于治疗至少部分特征为过度、异常或不适当血管生成的疾病。这些疾病状态包括但不限于癌症、糖尿病视网膜病变、黄斑变性和类风湿性关节炎。这些化合物通过抑制酪氨酸激酶受体酶，特别是KDR，并以不可逆的方式与KDR结合来抑制血管生成。
• Bis-quinazoline derivatives as inhibitors for epidermal growth factor receptor (EGFR) tyrosine kinase
  申请人：Tetranov International, Inc.

  公开号：US08916572B2

  公开（公告）日：2014-12-23

  Novel bis-quinazoline derivatives as tyrosine kinase inhibitors, synthesis of these compounds, and novel methods for treating tyrosine kinase mediated diseases or disorders using these compounds are disclosed. In particular, the present invention provides tethered quinazoline derivative dimers as inhibitors to the epidermal growth factor receptor (EGFR) tyrosine kinase, pharmaceutical compositions thereof, and their therapeutic uses for treating EGFR kinase-mediated diseases or disorders, such as various cancers, as well as synthetic methods for preparing these novel compounds.

  本发明揭示了一种新型的双喹唑啉衍生物，作为酪氨酸激酶抑制剂，合成这些化合物以及使用这些化合物治疗酪氨酸激酶介导的疾病或障碍的新方法。具体而言，本发明提供了连接的喹唑啉衍生物二聚体作为表皮生长因子受体（EGFR）酪氨酸激酶的抑制剂，以及其制药组成物和治疗使用，用于治疗EGFR激酶介导的疾病或障碍，如各种癌症，以及制备这些新化合物的合成方法。
• [EN] QUINONE SUBSTITUTED QUINAZOLINE AND QUINOLINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE QUINAZOLINE ET QUINOLINE KINASE A SUBSTITUTION QUINONE
  申请人：WYETH CORP

  公开号：WO2005115145A3

  公开（公告）日：2006-02-23
• US8916572B2
  申请人：——

  公开号：US8916572B2

  公开（公告）日：2014-12-23