1-{4-[(3-chlorophenyl)amino-6-quinazolinyl}-3-{2-[N-(2-chloroethyl)-N-methylethylenamine]}triazene | 871704-63-1

• 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: 1-{4-[(3-chlorophenyl)amino-6-quinazolinyl}-3-{2-[N-(2-chloroethyl)-N-methylethylenamine]}triazene
• 英文别名: 6-N-[2-[2-chloroethyl(methyl)amino]ethyldiazenyl]-4-N-(3-chlorophenyl)quinazoline-4,6-diamine
• CAS: 871704-63-1
• 化学式: C₁₉H₂₁Cl₂N₇
• 分子量: 418.329
• InChiKey: DGNJMLWWGCSXDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-{4-[(3-chlorophenyl)amino-6-quinazolinyl}-3-{2-[N-(2-chloroethyl)-N-methylethylenamine]}triazene 在 水 、 nitrosonium tetrafluoroborate 作用下， 以 乙腈 为溶剂， 反应 1.5h， 生成 6-N-[2-[benzyl(2-chloroethyl)amino]ethyldiazenyl]-4-N-(3-chlorophenyl)quinazoline-4,6-diamine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm070144p
• 作为产物：
  描述：

  6-N-[2-[N-(2-chloroethyl)-4-methoxyanilino]ethyldiazenyl]-4-N-(3-chlorophenyl)quinazoline-4,6-diamine 在 水 、 nitrosonium tetrafluoroborate 作用下， 以 乙腈 为溶剂， 反应 1.5h， 生成 1-{4-[(3-chlorophenyl)amino-6-quinazolinyl}-3-{2-[N-(2-chloroethyl)-N-methylethylenamine]}triazene
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm070144p

文献信息

• Novel combi-molecules having EGFR and DNA targeting properties
  申请人：Jean-Claude Bertrand

  公开号：US20060003970A1

  公开（公告）日：2006-01-05

  A series of new chemical agents that demonstrate anti-tumor activity are described. The new chemical agents combine two major mechanisms of anti-tumor action. In an embodiment, the agents are capable of both inhibiting EGFR and damaging DNA while also, upon degradation, degrading to an inhibitor of EGFR and to an agent capable of damaging DNA. Moreover, a novel series of molecules capable of releasing two moles of EGFR inhibitor and a potent bi-functional alkylating agent are also described.

  描述了一系列展示抗肿瘤活性的新化学试剂。这些新化学试剂结合了两种主要的抗肿瘤作用机制。在一个实施例中，这些试剂既能够抑制EGFR又能够损伤DNA，同时，在降解时，会降解为EGFR抑制剂和能够损伤DNA的试剂。此外，还描述了一系列新颖的分子，能够释放两摩尔的EGFR抑制剂和一种强效的双功能烷基化剂。
• US7879861B2
  申请人：——

  公开号：US7879861B2

  公开（公告）日：2011-02-01
• 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.