SMA 41 | 342655-59-8

• 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: SMA 41
• 英文别名: 1-[4-(m-tolyl)amino-6-quinazolinyl]-3-methyl triazene；6-N-(methyldiazenyl)-4-N-(3-methylphenyl)quinazoline-4,6-diamine
• CAS: 342655-59-8
• 化学式: C₁₆H₁₆N₆
• 分子量: 292.343
• InChiKey: LVSKRGBRYXZIRX-UHFFFAOYSA-N

物化性质

• 熔点：
  75-80 °C (decomp)
• 沸点：
  461.4±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  SMA 41 在 乙腈 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以obtained from the serial dilution of independently synthesized SMA52的产率得到N⁴-(m-tolyl)quinazoline-4,6-diamine
  参考文献：
  名称：

  Combi-molecules having signal transduction inhibitory properties and dna damaging properties

  摘要：

  本发明涉及一系列新的化学药剂，具有抗肿瘤活性。更具体地说，本发明涉及分子，称为“组合分子”，它们结合了两种主要的抗肿瘤作用机制。组合分子能够降解为细胞信号通路中涉及的配体和能够损伤DNA的药剂。更具体地说，本发明涉及能够阻止表皮生长因子受体（EGFR）介导的信号转导并能够损伤DNA的分子。本发明还涉及这些组合分子的一般合成方法。

  公开号：

  US20040086907A1
• 作为产物：
  描述：

  甲胺 、 N⁴-(m-tolyl)quinazoline-4,6-diamine 在 nitrosonium tetrafluoroborate 、 溶剂黄146 、 potassium carbonate 作用下， 以 乙腈 、 水 为溶剂， 以60%的产率得到SMA 41
  参考文献：
  名称：

  Synthesis of 1-[4-(m-tolyl)amino-6-quinazolinyl]-3-[14C]-methyl triazene: a radiolabeled probe for the combi-targeting concept

  摘要：

  本文介绍了 1-[4-(间甲苯基)氨基-6-喹唑啉基]-3-[14C]-甲基三嗪（SMA41）的合成。这种三嗪被设计成在生理条件下水解成 N4-间甲苯基喹唑啉-4,6-二胺（SMA52），它是表皮生长因子受体（EGFR）和 DNA 烷基化物种 [14C]-methyldiazonium 的中度抑制剂。我们需要一种放射性标记探针来验证 SMA41 原位水解可能诱导表皮生长因子受体 ATP 结合位点烷基化的假设。经 HPLC 定量和闪烁计数测定，14C-SMA41 的放射化学收率为 21%，比活度为 54.6 mCi/mmol。放射性-液相色谱分析显示放射性纯度为 98%。Copyright © 2003 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.713

文献信息

• Combi-molecules having signal transduction inhibitory properties and dna damaging properties
  申请人：——

  公开号：US20040086907A1

  公开（公告）日：2004-05-06

  The present invention relates to a series of new chemical agents that demonstrate anti-tumor activity. More particularly, the present invention relates to molecules, referred to as “combi-molecules”, that combine two major mechanisms of anti-tumor action. A combi-molecule is capable of degrading to a ligand involved in cell signaling pathways and to an agent capable of damaging DNA. More specifically, the present invention relates to molecules capable of blocking epidermal growth factor receptor (EGFR) mediated signal transduction and capable of damaging DNA. The present invention also relates to a general method of synthesis of these combi-molecules.

  本发明涉及一系列新的化学药剂，具有抗肿瘤活性。更具体地说，本发明涉及分子，称为“组合分子”，它们结合了两种主要的抗肿瘤作用机制。组合分子能够降解为细胞信号通路中涉及的配体和能够损伤DNA的药剂。更具体地说，本发明涉及能够阻止表皮生长因子受体（EGFR）介导的信号转导并能够损伤DNA的分子。本发明还涉及这些组合分子的一般合成方法。
• Synthesis of a Prodrug Designed To Release Multiple Inhibitors of the Epidermal Growth Factor Receptor Tyrosine Kinase and an Alkylating Agent:  A Novel Tumor Targeting Concept
  作者：Ranjita Banerjee、Zakaria Rachid、James McNamee、Bertrand J. Jean-Claude

  DOI：10.1021/jm030423m

  日期：2003.12.1

  The synthesis of a novel acetoxymethyltriazene designed to be a prodrug of multiple inhibitors of the epidermal growth factor receptor (EGFR) and a methyldiazonium species is described. Studies with each of the expected metabolites demonstrated significant EGFR tyrosine kinase inhibitory activities and the released methyldiazonium was trapped with p-nitrobenzylpyridine. Their ability to damage genomic DNA in whole cells was demonstrated by using the single cell microelectrophoresis (comet) assay. The results suggest that this approach may well represent a novel drug combination strategy involving single molecules masking multiple bioactive agents.
• US7572798B2
  申请人：——

  公开号：US7572798B2

  公开（公告）日：2009-08-11
• Synthesis of 1-[4-(m-tolyl)amino-6-quinazolinyl]-3-[14C]-methyl triazene: a radiolabeled probe for the combi-targeting concept
  作者：Stephanie L. Matheson、Shadreck Mzengeza、Bertrand J. Jean-Claude

  DOI：10.1002/jlcr.713

  日期：2003.7

  The synthesis of 1-[4-(m-tolyl)amino-6-quinazolinyl]-3-[14C]-methyl triazene (SMA41) is described. This triazene was designed to be hydrolyzed under physiological conditions to N4-m-tolyl-quinazoline-4,6-diamine (SMA52), a moderate inhibitor of the epidermal growth factor receptor (EGFR) and the DNA alkylating species [14C]-methyldiazonium. A radiolabeled probe was needed to test the hypothesis that in situ hydrolysis of SMA41 may induce alkylation of the ATP binding site of EGFR. 14C-SMA41 was obtained with a radiochemical yield of 21% and a specific activity of 54.6 mCi/mmol, as determined by HPLC quantitation and scintillation counting. Radio-TLC analyses showed 98% radiochemical purity. Copyright © 2003 John Wiley & Sons, Ltd.

  本文介绍了 1-[4-(间甲苯基)氨基-6-喹唑啉基]-3-[14C]-甲基三嗪（SMA41）的合成。这种三嗪被设计成在生理条件下水解成 N4-间甲苯基喹唑啉-4,6-二胺（SMA52），它是表皮生长因子受体（EGFR）和 DNA 烷基化物种 [14C]-methyldiazonium 的中度抑制剂。我们需要一种放射性标记探针来验证 SMA41 原位水解可能诱导表皮生长因子受体 ATP 结合位点烷基化的假设。经 HPLC 定量和闪烁计数测定，14C-SMA41 的放射化学收率为 21%，比活度为 54.6 mCi/mmol。放射性-液相色谱分析显示放射性纯度为 98%。Copyright © 2003 John Wiley & Sons, Ltd. All Rights Reserved.
• Combi-molecules having signal transduction inhibitory properties and DNA damaging properties
  申请人：McGill University

  公开号：US07572798B2

  公开（公告）日：2009-08-11

  The present invention relates to a series of new chemical agents that demonstrate anti-tumor activity. More particularly, the present invention relates to molecules, referred to as “combi-molecules”, that combine two major mechanisms of anti-tumor action. A combi-molecule is capable of degrading to a ligand involved in cell signaling pathways and to an agent capable of damaging DNA. More specifically, the present invention relates to molecules capable of blocking epidermal growth factor receptor (EGFR) mediated signal transduction and capable of damaging DNA. The present invention also relates to a general method of synthesis of these combi-molecules.

  本发明涉及一系列新的化学药剂，具有抗肿瘤活性。更具体地说，本发明涉及分子，称为“组合分子”，它们结合了两种主要的抗肿瘤作用机制。组合分子能够降解为参与细胞信号通路的配体和能够损伤DNA的药剂。更具体地说，本发明涉及能够阻止表皮生长因子受体（EGFR）介导的信号转导并能够损伤DNA的分子。本发明还涉及这些组合分子的一般合成方法。