2-{{[5-(4-{3-chloro-4-[(3-fluorobenzyl)oxy]anilino}-6-quinazolinyl)-furan-2-yl]methyl}[2-(methylsulfonyl)ethyl]amino}acetonitrile

• 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: 2-{{[5-(4-{3-chloro-4-[(3-fluorobenzyl)oxy]anilino}-6-quinazolinyl)-furan-2-yl]methyl}[2-(methylsulfonyl)ethyl]amino}acetonitrile
• 英文别名: 2-{{[5-(4-{3-chloro-4-[(3-fluorobenzyl)oxy]anilino}-6-quinazolinyl)-2-furyl]methyl}[2-(methylsulfonyl)ethyl]amino}acetonitrile；2-(((5-(4-(4-(3-Fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)furan-2-yl)methyl)(2-(methylsulfonyl)ethyl)amino)acetonitrile；2-[[5-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]furan-2-yl]methyl-(2-methylsulfonylethyl)amino]acetonitrile
• 化学式: C₃₁H₂₇ClFN₅O₄S
• 分子量: 620.104
• InChiKey: JGUKCUUOQNQOBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-氯-6-碘喹唑啉 在 palladium diacetate 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 2-{{[5-(4-{3-chloro-4-[(3-fluorobenzyl)oxy]anilino}-6-quinazolinyl)-furan-2-yl]methyl}[2-(methylsulfonyl)ethyl]amino}acetonitrile
  参考文献：
  名称：

  Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series

  摘要：

  Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme activity, but appeared to dramatically affect the cellular efficacy. The discovery of lapatinib emerged from this work. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.090

文献信息

• Anilinoquinazolines as protein tyrosine kinase inhibitors
  申请人：Cockerill George Stuart

  公开号：US06933299B1

  公开（公告）日：2005-08-23

  Heteroaromatic compounds are described, methods for their preparation, pharmaceutical compositions containing them, methods of use, and their use in medicines. In particular, the invention relates to quinazoline and pyridopyrimidine derivatives which exhibit protein tyrosine kinase inhibition.

  杂环芳香族化合物被描述，包括它们的制备方法、含有它们的药物组合物、使用方法以及它们在药物中的用途。特别是，本发明涉及喹唑啉和吡啶嘧啶衍生物，这些衍生物表现出蛋白酪氨酸激酶的抑制作用。
• Anilinoquinazaolines as protein tyrosine kianse inhibitors
  申请人：Cockerill Stuart George

  公开号：US20050143401A1

  公开（公告）日：2005-06-30

  Heteroaromatic compounds are described, methods for their preparation, pharmaceutical compositions containing them, methods of use, and their use in medicines. In particular, the invention relates to quinazoline and pyridopyrimidine derivatives which exhibit protein tyrosine kinase inhibition.

  本发明描述了杂环芳香化合物，它们的制备方法，含有它们的药物组合物，使用方法以及它们在药物中的应用。特别是，本发明涉及表现出蛋白酪氨酸激酶抑制活性的喹唑啉和吡啶嘧啶衍生物。
• [EN] CANCER TREATMENT METHOD<br/>[FR] METHODE DE TRAITEMENT DU CANCER
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005046678A1

  公开（公告）日：2005-05-26

  The present invention relates to a method of treating cancer in a mammal and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering an erb family inhibitor and a PI3K and/or Akt inhibitor to a mammal suffering from a cancer.

  本发明涉及一种治疗哺乳动物癌症的方法以及在这种治疗中有用的药物组合。具体而言，该方法涉及一种癌症治疗方法，其中向患有癌症的哺乳动物施用一种erb家族抑制剂和一种PI3K和/或Akt抑制剂。
• Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor
  申请人：Spector Lee Neil

  公开号：US20050176740A1

  公开（公告）日：2005-08-11

  The present invention relates to a method of treating cancer in a mammal and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering an erb family inhibitor and a Raf and/or ras inhibitor to a mammal suffering from a cancer.

  本发明涉及一种治疗哺乳动物癌症的方法和在这种治疗中有用的药物组合。具体来说，该方法涉及一种癌症治疗方法，包括向患有癌症的哺乳动物施用erb家族抑制剂和Raf和/或ras抑制剂。
• HETEROCYCLIC COMPOUNDS
  申请人：Cockerill Stuart George

  公开号：US20080004294A1

  公开（公告）日：2008-01-03

  Heteroaromatic compounds are described, methods for their preparation, pharmaceutical compositions containing them, methods of use, and their use in medicines. In particular, the invention relates to quinazoline and pyridopyrimidine derivatives which exhibit protein tyrosine kinase inhibition.

  本发明涉及杂环芳香化合物、其制备方法、含有它们的药物组合物、使用方法以及它们在药物中的应用。特别地，本发明涉及能够抑制蛋白酪氨酸激酶的喹嗪啉和吡啶并嘧啶衍生物。