(4-(3-fluorobenzyloxy)-3-chlorophenyl)-(6-(2-((2-(2-N-methylimidazolyl)-sulphonyl-ethylamino)-methyl)-furan-2-yl)-quinazolin-4-yl)-amine

• 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: (4-(3-fluorobenzyloxy)-3-chlorophenyl)-(6-(2-((2-(2-N-methylimidazolyl)-sulphonyl-ethylamino)-methyl)-furan-2-yl)-quinazolin-4-yl)-amine
• 英文别名: N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[[2-(1-methylimidazol-2-yl)sulfonylethylamino]methyl]furan-2-yl]quinazolin-4-amine
• 化学式: C₃₂H₂₈ClFN₆O₄S
• 分子量: 647.13
• InChiKey: QDJORKXCLNITAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  133
• 氢给体数：
  2
• 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 、 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 (4-(3-fluorobenzyloxy)-3-chlorophenyl)-(6-(2-((2-(2-N-methylimidazolyl)-sulphonyl-ethylamino)-methyl)-furan-2-yl)-quinazolin-4-yl)-amine
  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

• 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。
• US7189734B2
  申请人：——

  公开号：US7189734B2

  公开（公告）日：2007-03-13
• US7265123B2
  申请人：——

  公开号：US7265123B2

  公开（公告）日：2007-09-04
• US7507741B2
  申请人：——

  公开号：US7507741B2

  公开（公告）日：2009-03-24
• Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series
  作者：Kimberly G. Petrov、Yue-Mei Zhang、Malcolm Carter、G. Stuart Cockerill、Scott Dickerson、Cassandra A. Gauthier、Yu Guo、Robert A. Mook、David W. Rusnak、Ann L. Walker、Edgar R. Wood、Karen E. Lackey

  DOI：10.1016/j.bmcl.2006.05.090

  日期：2006.9

  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.