3-(5-{4-[4-(benzyloxy)-3-chloroanilino]-6-quinazolinyl}-furan-2-yl)-2-propenoic acid | 320337-39-1

• 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: 3-(5-{4-[4-(benzyloxy)-3-chloroanilino]-6-quinazolinyl}-furan-2-yl)-2-propenoic acid
• 英文别名: 3-(5-{4-[4-(Benzyloxy)-3-chloroanilino]-6-quinazolinyl}-2-furyl)-2-propenoic acid；3-[5-[4-(3-chloro-4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]prop-2-enoic acid
• CAS: 320337-39-1
• 化学式: C₂₈H₂₀ClN₃O₄
• 分子量: 497.938
• InChiKey: VWXAOKSIDRKHKV-UHFFFAOYSA-N

物化性质

• 沸点：
  697.5±55.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  97.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(5-{4-[4-(benzyloxy)-3-chloroanilino]-6-quinazolinyl}-furan-2-yl)-2-propenoic acid 在 dimethyl sulfide borane 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成
  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
• 作为产物：
  描述：

  4-苄氧基-3-氯硝基苯 在 platinum on activated charcoal palladium diacetate 、 sodium hydroxide 、 氢气 、 potassium carbonate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 生成 3-(5-{4-[4-(benzyloxy)-3-chloroanilino]-6-quinazolinyl}-furan-2-yl)-2-propenoic acid
  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：US20060189637A1

  公开（公告）日：2006-08-24

  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、含有它们的制药组合物、使用方法以及它们在药物中的应用。具体而言，本发明涉及具有蛋白酪氨酸激酶抑制作用的喹嗪啉和吡啶并嘧啶衍生物。
• Heterocyclic compounds
  申请人：SmithKline Beecham Corporation

  公开号：US07265123B2

  公开（公告）日：2007-09-04

  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、其制备方法、包含它们的制药组合物、使用方法以及它们在药物中的应用。特别地，该发明涉及对蛋白酪氨酸激酶抑制作用的喹唑啉和吡啶并嘧啶衍生物。
• 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。