N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-(piperidin-1-ylmethyl)phenyl)quinazolin-4-amine | 1432450-91-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-(piperidin-1-ylmethyl)phenyl)quinazolin-4-amine
• 英文别名: NEU-0000787；N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[4-(piperidin-1-ylmethyl)phenyl]quinazolin-4-amine
• CAS: 1432450-91-3
• 化学式: C₃₃H₃₀ClFN₄O
• 分子量: 553.079
• InChiKey: BIEGSRZCMNHTRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  50.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-碘-4(H)-喹唑啉酮 在 四(三苯基膦)钯 、 氯化亚砜 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 36.0h， 生成 N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-(piperidin-1-ylmethyl)phenyl)quinazolin-4-amine
  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