(4-(3-fluorobenzyloxy)-3-chlorophenyl)-(6-(2-((2-phenylsulphonyl-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-phenylsulphonyl-ethylamino)-methyl)-furan-2-yl)-quinazolin-4-yl)-amine
• 英文别名: N-(3-Chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-(phenylsulfonyl)ethyl)amino)methyl)furan-2-yl)quinazolin-4-amine；6-[5-[[2-(benzenesulfonyl)ethylamino]methyl]furan-2-yl]-N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]quinazolin-4-amine
• 化学式: C₃₄H₂₈ClFN₄O₄S
• 分子量: 643.138
• InChiKey: MTHDVQYDQJZAFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  9

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-phenylsulphonyl-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

• US7189734B2
  申请人：——

  公开号：US7189734B2

  公开（公告）日：2007-03-13
• 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.