3-chloro-4-((2,3-difluorobenzyl)oxy)aniline | 1153434-95-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-chloro-4-((2,3-difluorobenzyl)oxy)aniline
• 英文别名: 3-Chloro-4-[(2,3-difluorophenyl)methoxy]aniline
• CAS: 1153434-95-7
• 化学式: C₁₃H₁₀ClF₂NO
• mdl: MFCD12110848
• 分子量: 269.678
• InChiKey: SWDYQMOTUFBBNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-chloro-4-((2,3-difluorobenzyl)oxy)aniline 、 4-((4-(4-chloroquinazolin-6-yl)phenyl)sulfonyl)morpholine hydrochloride 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以53.3%的产率得到N-[3-chloro-4-[(2,3-difluorophenyl)methoxy]phenyl]-6-(4-morpholin-4-ylsulfonylphenyl)quinazolin-4-amine;hydrochloride
  参考文献：
  名称：

  Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis

  摘要：

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.

  DOI：

  10.1021/jm400349k
• 作为产物：
  描述：

  2-氯-4-硝基苯酚 在 potassium carbonate 、 氯化铵 、 锌 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 18.0h， 生成 3-chloro-4-((2,3-difluorobenzyl)oxy)aniline
  参考文献：
  名称：

  Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis

  摘要：

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.

  DOI：

  10.1021/jm400349k

文献信息

• PROTOZOAN PARASITE GROWTH INHIBITORS
  申请人：Northeastern University

  公开号：US20150259331A1

  公开（公告）日：2015-09-17

  Compounds and methods for inhibiting growth of a protozoan parasite. Methods of treating a protozoan parasite infection in a subject by administering a therapeutically effective amount of a compound as disclosed herein. The compounds and methods can be used to inhibit growth of protozoan parasites such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., and Plasmodium spp.

  用于抑制原生动物寄生虫生长的化合物和方法。通过向主体施用如本文所述的治疗有效量的化合物来治疗原生动物寄生虫感染的方法。这些化合物和方法可用于抑制如非洲锥虫、克鲁兹锥虫、利什曼原虫属和疟原虫属等原生动物寄生虫的生长。
• Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis
  作者：Gautam Patel、Caitlin E. Karver、Ranjan Behera、Paul J. Guyett、Catherine Sullenberger、Peter Edwards、Norma E. Roncal、Kojo Mensa-Wilmot、Michael P. Pollastri

  DOI：10.1021/jm400349k

  日期：2013.5.23

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.