(6-iodo-((4-benzyloxy)-3-chlorophenyl)-quinazolin-4-yl)amine | 320337-46-0

• 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: (6-iodo-((4-benzyloxy)-3-chlorophenyl)-quinazolin-4-yl)amine
• 英文别名: N-(3-chloro-4-phenylmethoxyphenyl)-6-iodoquinazolin-4-amine
• CAS: 320337-46-0
• 化学式: C₂₁H₁₅ClIN₃O
• 分子量: 487.727
• InChiKey: PGNQRVZNCUJEKZ-UHFFFAOYSA-N

物化性质

• 沸点：
  583.5±50.0 °C(Predicted)
• 密度：
  1.654±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6-iodo-((4-benzyloxy)-3-chlorophenyl)-quinazolin-4-yl)amine 在 palladium diacetate 、 sodium hydroxide 、 potassium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 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 氢气 作用下， 以 四氢呋喃 、 乙醇 、 异丙醇 为溶剂， 生成 (6-iodo-((4-benzyloxy)-3-chlorophenyl)-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

• 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。
• Discovery and Biological Evaluation of Potent Dual ErbB-2/EGFR Tyrosine Kinase Inhibitors: 6-Thiazolylquinazolines
  作者：Micheal D Gaul、Yu Guo、Karen Affleck、G.Stuart Cockerill、Tona M Gilmer、Robert J Griffin、Stephen Guntrip、Barry R Keith、Wilson B Knight、Robert J Mullin、Doris M Murray、David W Rusnak、Kathryn Smith、Sarva Tadepalli、Edgar R Wood、Karen Lackey

  DOI：10.1016/s0960-894x(02)01047-8

  日期：2003.2

  We have identified a novel class of 6-thiazolylquinazolines as potent and selective inhibitors of both ErbB-2 and EGFR tyrosine kinase activity, with IC50 values in the nanomolar range. These compounds inhibited the growth of both EGFR (HN5) and ErbB-2 (BT474) over-expressing human tumor cell lines in vitro. Using xenograft models of the same cell lines. we found that the compounds given orally inhibited in vivo tumor growth significantly compared with control animals. (C) 2003 Elsevier Science Ltd. All rights reserved.
• LAPATINIB INTERMEDIATES
  申请人：METSGER Leonid

  公开号：US20100197915A1

  公开（公告）日：2010-08-05

  The invention provides lapatinib intermediates and improved processes for preparing lapatinib intermediates. The invention also provides processes for preparing lapatinib base and lapatinib ditosylate.
• [EN] LAPATINIB INTERMEDIATES<br/>[FR] INTERMÉDIAIRES DE LAPATINIB
  申请人：TEVA PHARMA

  公开号：WO2010017387A2

  公开（公告）日：2010-02-11

  The invention provides lapatinib intermediates and improved processes for preparing lapatinib intermediates. The invention also provides processes for preparing lapatinib base and lapatinib ditosylate.