拉帕替尼杂质K | 231278-83-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 拉帕替尼杂质K
• 英文名称: 5-(4-{3-chloro-4-benzyloxyanilino}-6-quinazolinyl)-furan-2-carbaldehyde
• 英文别名: 5-(4-{3-chloro-4-benzyloxyanilino}-6-quinazolinyl)-2-furaldehyde；5-[4-(3-Chloro-4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-carbaldehyde
• CAS: 231278-83-4
• 化学式: C₂₆H₁₈ClN₃O₃
• 分子量: 455.9
• InChiKey: FSQQOQJTZOTQMX-UHFFFAOYSA-N

物化性质

• 沸点：
  652.6±55.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  拉帕替尼杂质K 在 sodium hydroxide 、 dimethyl sulfide borane 、 potassium carbonate 、 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 、 甲醇 、 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：

  2-氯-4-硝基苯酚 在 platinum on activated charcoal palladium diacetate 、 氢气 、 potassium carbonate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 生成 拉帕替尼杂质K
  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。
• Heterocyclic compounds
  申请人：——

  公开号：US20020147205A1

  公开（公告）日：2002-10-10

  The present invention relates to substituted heteroaromatic compounds, methods for their preparation, pharmaceutical compositions containing them and their use in medicine. Specifically, the invention relates to quinazoline derivatives useful in treating disorders mediated by protein tyrosine kinase activity, in particular erbB-2 and/or EGFR activity.

  本发明涉及替代杂环芳香化合物，其制备方法，包含它们的制药组合物以及它们在医学上的用途。具体而言，本发明涉及喹唑啉衍生物，用于治疗由蛋白酪氨酸激酶活性介导的紊乱，特别是erbB-2和/或EGFR活性。
• HETEROCYCLIC COMPOUNDS
  申请人：CARTER Clive Malcolm

  公开号：US20070238875A1

  公开（公告）日：2007-10-11

  A process for the preparation of a compound of formula (I) comprising the steps: (a) reacting a compound of formula (II) wherein L and L′ are suitable leaving groups, with a compound of formula (III) UNH 2 (III) to prepare a compound of formula (IV) and subsequently (b) substituting the group R 1 by replacement of the leaving group L′.

  一种制备化合物(I)的方法，包括以下步骤：（a）将式为(II)的化合物与式为(III)的化合物UNH2(III)反应，其中L和L'是适当的离去基团，以制备式为(IV)的化合物；随后(b)通过替换离去基团L'来取代基团R1。
• BICYCLIC HETEROAROMATIC COMPOUNDS AS PROTEIN TYROSINE KINASE INHIBITORS
  申请人：GlaxoSmithKline LLC

  公开号：US20150065527A1

  公开（公告）日：2015-03-05

  A pharmaceutical formulation comprising the compound of formula

  一种药物配方，其中包含化学式的化合物。