1-(3-bromopropoxy)-2-chloro-4-nitrobenzene

• 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: 1-(3-bromopropoxy)-2-chloro-4-nitrobenzene
• 化学式: C₉H₉BrClNO₃
• 分子量: 294.532
• InChiKey: LJQYZKFIHBGVPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-bromopropoxy)-2-chloro-4-nitrobenzene 在 盐酸 、 三乙酰氧基硼氢化钠 、 铁粉 、 potassium carbonate 、 氯化铵 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 31.0h， 生成 4-({3-chloro-4-[3-(methyl-prop-2-ynyl-amino)-propoxy]-phenylamino}-methyl)-benzoic acid methyl ester
  参考文献：
  名称：

  N-Methylpropargylamine-Conjugated Hydroxamic Acids as Dual Inhibitors of Monoamine Oxidase A and Histone Deacetylase for Glioma Treatment

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c01726
• 作为产物：
  描述：

  2-氯-4-硝基苯酚 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以71%的产率得到1-(3-bromopropoxy)-2-chloro-4-nitrobenzene
  参考文献：
  名称：

  <p>Design, synthesis, and biological study of 4-[(2-nitroimidazole-1<em>H</em>-alkyloxyl)aniline]-quinazolines as EGFR inhibitors exerting cytotoxicities both under normoxia and hypoxia</p>

  摘要：

  Purpose: In order to get novel EGFR inhibitors exerting more potency in tumor hypoxia than in normoxia.Methods: A series of 4-[(2-nitroimidazole-1H-alkyloxyl)aniline]-quinazolines were designed and synthesized, and their in vitro cytotoxicity and EGFR inhibitory activity were evaluated. Molecule docking study was performed for the representative compound.Results: The structure-activity relationship (SAR) studies revealed that compounds bearing both meta-chloride and para-(2-nitroimidazole-1H-alkyloxy) groups on the aniline displayed potent inhibitory activities both in enzymatic and cellular levels. The most promising compound 16i potently inhibited EGFR with an IC50 value of 0.12 mu M. Meanwhile, it manifested more potent cytotoxicity than the positive control lapatinib under tumor normoxia and hypoxia conditions (IC50 values of 1.59 and 1.09 mu M against A549 cells, 2.46 and 1.35 mu M against HT-29 cells, respectively). The proposed binding model of 16i in complex with EGFR was displayed by the docking results.Conclusion: This study provides insights for developing hypoxia-activated kinase inhibitors.

  DOI：

  10.2147/dddt.s209481

文献信息

• Design, synthesis, and biological activity of dual monoamine oxidase A and heat shock protein 90 inhibitors, N-Methylpropargylamine-conjugated 4-isopropylresorcinol for glioblastoma
  作者：Hui-Ju Tseng、Suddhasatwa Banerjee、Bin Qian、Mei-Jung Lai、Tung-Yun Wu、Tsung-I Hsu、Tony Eight Lin、Kai-Cheng Hsu、Kuo-Hsiang Chuang、Jing-Ping Liou、Jean C. Shih

  DOI：10.1016/j.ejmech.2023.115459

  日期：2023.8
• <i>N</i>-Methylpropargylamine-Conjugated Hydroxamic Acids as Dual Inhibitors of Monoamine Oxidase A and Histone Deacetylase for Glioma Treatment
  作者：Samir Mehndiratta、Bin Qian、Jian-Ying Chuang、Jing-Ping Liou、Jean C. Shih

  DOI：10.1021/acs.jmedchem.1c01726

  日期：2022.2.10
• &lt;p&gt;Design, synthesis, and biological study of 4-[(2-nitroimidazole-1&lt;em&gt;H&lt;/em&gt;-alkyloxyl)aniline]-quinazolines as EGFR inhibitors exerting cytotoxicities both under normoxia and hypoxia&lt;/p&gt;
  作者：Weiyan Cheng、Suhua Wang、Zhiheng Yang、Xin Tain、Yongzhou Hu

  DOI：10.2147/dddt.s209481

  日期：——

  Purpose: In order to get novel EGFR inhibitors exerting more potency in tumor hypoxia than in normoxia.Methods: A series of 4-[(2-nitroimidazole-1H-alkyloxyl)aniline]-quinazolines were designed and synthesized, and their in vitro cytotoxicity and EGFR inhibitory activity were evaluated. Molecule docking study was performed for the representative compound.Results: The structure-activity relationship (SAR) studies revealed that compounds bearing both meta-chloride and para-(2-nitroimidazole-1H-alkyloxy) groups on the aniline displayed potent inhibitory activities both in enzymatic and cellular levels. The most promising compound 16i potently inhibited EGFR with an IC50 value of 0.12 mu M. Meanwhile, it manifested more potent cytotoxicity than the positive control lapatinib under tumor normoxia and hypoxia conditions (IC50 values of 1.59 and 1.09 mu M against A549 cells, 2.46 and 1.35 mu M against HT-29 cells, respectively). The proposed binding model of 16i in complex with EGFR was displayed by the docking results.Conclusion: This study provides insights for developing hypoxia-activated kinase inhibitors.