1-Azido-4,5-dimethyl-2-nitro-benzene | 1027598-42-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-Azido-4,5-dimethyl-2-nitro-benzene
• 英文别名: 1-Azido-4,5-dimethyl-2-nitrobenzene
• CAS: 1027598-42-0
• 化学式: C₈H₈N₄O₂
• 分子量: 192.177
• InChiKey: LUDTZTYDJAYXSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  60.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-Azido-4,5-dimethyl-2-nitro-benzene 以 甲苯 为溶剂， 反应 4.0h， 以2.29 g的产率得到5,6-二甲基-1-氧代-2,1,3-苯并恶二唑-1-鎓
  参考文献：
  名称：

  生物还原性3-取代喹喔啉二-N-氧化物的自由基化学和细胞毒性

  摘要：

  已经研究了一系列喹喔啉二氮氧化物（QDO）化合物的自由基化学和细胞毒性，以探索此类生物还原药物的作用机理。一系列的水溶性3-三氟甲基的（4 - 10），3-苯基（11 - 19），和3-甲基（20 - 21）取代的QDO化合物被设计为跨越一系列与生物还原相符的电子亲和力。厌氧甲酸水溶液缓冲液的稳态辐射分解对QDO的损失的化学计量表明，QDO的单电子还原会生成自由基，该自由基能够通过甲酸的氧化来引发链反应。如EPR自旋捕获实验所确定，3-三氟甲基类似物表现出与HO •释放一致的长链反应。几个碳中心自由基中间体，通过截断细胞色素P450还原酶（POR）使用，进行了表征具有N-末端的QDO化合物的厌氧培养产生ñ -叔丁基α苯基硝酮（PBN）和5-（二乙氧基磷酰基）-5- -甲基-1-吡咯啉-N氧化物（DEPMPO）自旋阱，并通过EPR进行了观察。对产生强氧化性自由基的实验数据进行了很好的模拟，这

  DOI：

  10.1021/acs.chemrestox.6b00133
• 作为产物：
  描述：

  3,4-二甲基乙酰苯胺 在 盐酸 、 sodium azide 、 硫酸 、 硝酸 、 sodium acetate 、 sodium nitrite 作用下， 反应 1.17h， 生成 1-Azido-4,5-dimethyl-2-nitro-benzene
  参考文献：
  名称：

  Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides

  摘要：

  Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy. Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy. The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells. Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and/or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells. Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced. Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxides have reduction potentials significantly more positive than Tirapazamine (E(pc)-0.90 V). The most potent cytotoxins to cells in culture were the 6,7,-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine. The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity. Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro. In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine. This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.

  DOI：

  10.1021/jm00010a023

文献信息

• Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
  作者：Antonio Monge、Juan A. Palop、Adela Lopez de Cerain、Virginia Senador、Francisco J. Martinez、Yolanda Sainz、Susana Narro、Estrella Garcia、Carlos de Miguel

  DOI：10.1021/jm00010a023

  日期：1995.5

  Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy. Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy. The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells. Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and/or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells. Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced. Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxides have reduction potentials significantly more positive than Tirapazamine (E(pc)-0.90 V). The most potent cytotoxins to cells in culture were the 6,7,-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine. The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity. Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro. In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine. This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
• Radical Chemistry and Cytotoxicity of Bioreductive 3-Substituted Quinoxaline Di-<i>N</i>-Oxides
  作者：Robert F. Anderson、Pooja Yadav、Sujata S. Shinde、Cho R. Hong、Susan M. Pullen、Jóhannes Reynisson、William R. Wilson、Michael P. Hay

  DOI：10.1021/acs.chemrestox.6b00133

  日期：2016.8.15

  oxidizing radicals, capable of H atom abstraction from methyl groups. The kinetics of formation and decay of the radicals produced following one-electron reduction of the parent compounds, both in oxic and anoxic solutions, were determined using pulse radiolysis. Back oxidation of the initially formed radical anions by molecular oxygen did not compete effectively with the breakdown of the radical anions

  已经研究了一系列喹喔啉二氮氧化物（QDO）化合物的自由基化学和细胞毒性，以探索此类生物还原药物的作用机理。一系列的水溶性3-三氟甲基的（4 - 10），3-苯基（11 - 19），和3-甲基（20 - 21）取代的QDO化合物被设计为跨越一系列与生物还原相符的电子亲和力。厌氧甲酸水溶液缓冲液的稳态辐射分解对QDO的损失的化学计量表明，QDO的单电子还原会生成自由基，该自由基能够通过甲酸的氧化来引发链反应。如EPR自旋捕获实验所确定，3-三氟甲基类似物表现出与HO •释放一致的长链反应。几个碳中心自由基中间体，通过截断细胞色素P450还原酶（POR）使用，进行了表征具有N-末端的QDO化合物的厌氧培养产生ñ -叔丁基α苯基硝酮（PBN）和5-（二乙氧基磷酰基）-5- -甲基-1-吡咯啉-N氧化物（DEPMPO）自旋阱，并通过EPR进行了观察。对产生强氧化性自由基的实验数据进行了很好的模拟，这