ZR2003

• 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: ZR2003
• 英文别名: N*6*-(2-Chloro-ethyl)-N*4*-(3-chloro-phenyl)-quinazoline-4,6-diamine；6-N-(2-chloroethyl)-4-N-(3-chlorophenyl)quinazoline-4,6-diamine
• 化学式: C₁₆H₁₄Cl₂N₄
• 分子量: 333.22
• InChiKey: RGZBNUZXRSSFQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 五氯化磷 、 硫酸 、 铁粉 、 nitrosonium tetrafluoroborate 、 溶剂黄146 作用下， 以 乙醇 、 异丙醇 、 乙腈 为溶剂， 生成 ZR2003
  参考文献：
  名称：

  Synthesis of half-mustard combi-molecules with fluorescence properties: correlation with EGFR status

  摘要：

  The synthesis of 6-(2-chloroethylamino)-4-anilinoquinazolines ZR2002 and ZR2003 designed to block EGFR tyrosine kinase and to damage genomic DNA is described. These compounds present fluorescence properties that permitted the quantitation of their subcellular uptake by flow cytometry. Fluorescence intensities increased with increasing levels of EGFR in a panel of isogenic and established cell lines. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.12.015

文献信息

• Novel Nitrogen Mustard-Armed Combi-Molecules for the Selective Targeting of Epidermal Growth Factor Receptor Overexperessing Solid Tumors:  Discovery of an Unusual Structure−Activity Relationship
  作者：Zakaria Rachid、Fouad Brahimi、Qiyu Qiu、Christopher Williams、Janet M. Hartley、John A. Hartley、Bertrand J. Jean-Claude

  DOI：10.1021/jm070144p

  日期：2007.5.1

  To enhance the potency of "combi-molecules", we designed 6a-d and 18 to release an inhibitor of EGFR TK and a bifunctional alkylator. The combi-molecules blocked EGFR TK with potency increasing with the basicity of the mustard moiety. They selectively killed cells transfected with EGFR and were potent against the DU145 prostate cancer cells. Combi-molecule 6a blocked EGFR phosphorylation in an irreversible manner, induced DNA-cross-links, and arrested the cells in mid-S.
• US7879861B2
  申请人：——

  公开号：US7879861B2

  公开（公告）日：2011-02-01
• Synthesis of half-mustard combi-molecules with fluorescence properties: correlation with EGFR status
  作者：Zakaria Rachid、Fouad Brahimi、Juozas Domarkas、Bertrand Jacques Jean-Claude

  DOI：10.1016/j.bmcl.2004.12.015

  日期：2005.2

  The synthesis of 6-(2-chloroethylamino)-4-anilinoquinazolines ZR2002 and ZR2003 designed to block EGFR tyrosine kinase and to damage genomic DNA is described. These compounds present fluorescence properties that permitted the quantitation of their subcellular uptake by flow cytometry. Fluorescence intensities increased with increasing levels of EGFR in a panel of isogenic and established cell lines. (C) 2004 Elsevier Ltd. All rights reserved.