N-(4-(3-bromoanilino)quinazolin-6-yl)-4-chlorobutanamide | 1453102-06-1

• 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-(3-bromoanilino)quinazolin-6-yl)-4-chlorobutanamide
• 英文别名: N-[4-(3-bromoanilino)quinazolin-6-yl]-4-chlorobutanamide
• CAS: 1453102-06-1
• 化学式: C₁₈H₁₆BrClN₄O
• 分子量: 419.708
• InChiKey: UGNDXEZCADEHES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  66.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  哌啶 、 N-(4-(3-bromoanilino)quinazolin-6-yl)-4-chlorobutanamide 反应 24.0h， 以41%的产率得到N-(4-(3-bromoanilino)quinazolin-6-yl)-4-(piperidin-1-yl)butanamide
  参考文献：
  名称：

  Long-lasting inhibition of EGFR autophosphorylation in A549 tumor cells by intracellular accumulation of non-covalent inhibitors

  摘要：

  In the present study, a small set of reversible or irreversible 4-anilinoquinazoline EGFR inhibitors was tested in A549 cells at early (1 h) and late (8 h) time points after inhibitor removal from culture medium. A combination of assays was employed to explain the observed long-lasting inhibition of EGFR autophosphorylation. We found that EGFR inhibition at 8 h can be due, besides to the covalent interaction of the inhibitor with Cys797, as for PD168393 (2) and its prodrug 4, to the intracellular accumulation of non-covalent inhibitors by means of an active cell uptake, as for 5 and 6. Compounds 5-6 showed similar potency and duration of inhibition of EGFR autophosphorylation as the covalent inhibitor 2, while being devoid of reactive groups forming covalent bonds with protein thiols. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.008
• 作为产物：
  描述：

  N4-(3-溴苯基)喹唑啉-4,6-二胺 、 4-氯丁酰氯 反应 16.0h， 以82%的产率得到N-(4-(3-bromoanilino)quinazolin-6-yl)-4-chlorobutanamide
  参考文献：
  名称：

  Long-lasting inhibition of EGFR autophosphorylation in A549 tumor cells by intracellular accumulation of non-covalent inhibitors

  摘要：

  In the present study, a small set of reversible or irreversible 4-anilinoquinazoline EGFR inhibitors was tested in A549 cells at early (1 h) and late (8 h) time points after inhibitor removal from culture medium. A combination of assays was employed to explain the observed long-lasting inhibition of EGFR autophosphorylation. We found that EGFR inhibition at 8 h can be due, besides to the covalent interaction of the inhibitor with Cys797, as for PD168393 (2) and its prodrug 4, to the intracellular accumulation of non-covalent inhibitors by means of an active cell uptake, as for 5 and 6. Compounds 5-6 showed similar potency and duration of inhibition of EGFR autophosphorylation as the covalent inhibitor 2, while being devoid of reactive groups forming covalent bonds with protein thiols. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.008

文献信息

• Long-lasting inhibition of EGFR autophosphorylation in A549 tumor cells by intracellular accumulation of non-covalent inhibitors
  作者：Federica Vacondio、Caterina Carmi、Elena Galvani、Michele Bassi、Claudia Silva、Alessio Lodola、Silvia Rivara、Andrea Cavazzoni、Roberta R. Alfieri、Pier Giorgio Petronini、Marco Mor

  DOI：10.1016/j.bmcl.2013.08.008

  日期：2013.10

  In the present study, a small set of reversible or irreversible 4-anilinoquinazoline EGFR inhibitors was tested in A549 cells at early (1 h) and late (8 h) time points after inhibitor removal from culture medium. A combination of assays was employed to explain the observed long-lasting inhibition of EGFR autophosphorylation. We found that EGFR inhibition at 8 h can be due, besides to the covalent interaction of the inhibitor with Cys797, as for PD168393 (2) and its prodrug 4, to the intracellular accumulation of non-covalent inhibitors by means of an active cell uptake, as for 5 and 6. Compounds 5-6 showed similar potency and duration of inhibition of EGFR autophosphorylation as the covalent inhibitor 2, while being devoid of reactive groups forming covalent bonds with protein thiols. (C) 2013 Elsevier Ltd. All rights reserved.