4-(2-bromoethoxy)-3-chloroaniline

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(2-bromoethoxy)-3-chloroaniline
• 英文别名: 1-(4-amino-2-chlorophenoxy)-2-bromoethane
• 化学式: C₈H₉BrClNO
• 分子量: 250.523
• InChiKey: WASWFCPFNDTXOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(2-bromoethoxy)-3-chloroaniline 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 12.0h， 生成 N-(3-chloro-4-(2-(2-nitro-1H-imidazol-1-yl)ethoxy)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
  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
• 作为产物：
  描述：

  2-氯-4-硝基苯酚 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~60.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成 4-(2-bromoethoxy)-3-chloroaniline
  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

• Amine derivatives, processes for producing them and a use of them as
  申请人：C&C Research Labs.

  公开号：US06057358A1

  公开（公告）日：2000-05-02

  Novel amine derivatives of the following general formula (I): ##STR1## (wherein) A may denote --(CH.sub.2)--O--, --(CH.sub.2).sub.2 --O--, or --(CH.sub.2).sub.2 --NH--; B may denote --(CH.sub.2).sub.2 --; R.sub.1 may denote a hydrogen atom, a halogen atom, a nitro group, a 1-pyrrolyl group, an acetamido group, an amino group or a dimethylamino group; R.sub.2 may denote a hydrogen atom or a nitro group; R.sub.3 and R.sub.4 may denote a hydrogen atom; R.sub.8a and R.sub.8b which are the same may denote a chlorine atom or a methoxy group; R.sub.9 may denote a hydrogen atom or an amino group; R may denote a methyl group; and X may denote a methanesulfonamido group, a 1-imidazolyl group or a nitro group or a salts thereof are useful as antiarrhythmic drugs.

  以下一般式（I）的新型胺衍生物：##STR1## 其中：A可以表示--(CH.sub.2)--O--, --(CH.sub.2).sub.2 --O--, 或--(CH.sub.2).sub.2 --NH--; B可以表示--(CH.sub.2).sub.2 --; R.sub.1可以表示氢原子、卤原子、硝基基团、1-吡咯基团、乙酰胺基团、氨基团或二甲胺基团; R.sub.2可以表示氢原子或硝基基团; R.sub.3和R.sub.4可以表示氢原子; R.sub.8a和R.sub.8b相同，可以表示氯原子或甲氧基团; R.sub.9可以表示氢原子或氨基团; R可以表示甲基基团; X可以表示甲磺酰氨基团、1-咪唑基团或硝基团或其盐，可用作抗心律失常药物。
• NOVEL AMINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE THEREOF AS ANTIARRHYTHMIC
  申请人：C & C RESEARCH LABS.

  公开号：EP0775689A1

  公开（公告）日：1997-05-28

  Novel amine derivatives of the following general formula (I): (wherei A may denote -(CH2)-O-, -(CH2)2-O-, or -(CH2)2-NH-; B may denote -(CH2)2-; R1 may denote a hydrogen atom, a halogen atom, a nitro group, a 1-pyrrolyl group, an acetamido group, an amino group or a dimethylamino group; R2 may denote a hydrogen atom or a nitro group; R3 and R4 may denote a hydrogen atom; R8a and R8b which are the same may denote a chlorine atom or a methoxy group; R9 may denote a hydrogen atom or an amino group; R may denote a methyl group; and X may denote a methanesulfonamido group, a 1-imidazolyl group or a nitro group or a salts thereof are useful as antiarrhythmic drugs.

  以下通式(I)的新型胺衍生物： (其中i A 可表示-(CH2)-O-、-(CH2)2-O-或-(CH2)2-NH-； B 可表示-(CH2)2-； R1 可表示氢原子、卤素原子、硝基、1-吡咯基、乙酰氨基、氨基或二甲基氨基； R2 可表示氢原子或硝基； R3 和 R4 可表示氢原子； 相同的 R8a 和 R8b 可表示氯原子或甲氧基； R9 可表示氢原子或氨基； R 可表示甲基 X 可表示甲磺酰胺基团、1-咪唑基团或硝基，或其盐类可用作抗心律失常药物。
• US6057358A
  申请人：——

  公开号：US6057358A

  公开（公告）日：2000-05-02
• &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.