1-Azido-2-nitro-4-trifluoromethoxy-benzene | 1025801-23-3

• 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-2-nitro-4-trifluoromethoxy-benzene
• 英文别名: 1-Azido-2-nitro-4-(trifluoromethoxy)benzene
• CAS: 1025801-23-3
• 化学式: C₇H₃F₃N₄O₃
• 分子量: 248.121
• InChiKey: NICNBZNEXOEEKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-Azido-2-nitro-4-trifluoromethoxy-benzene 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 26.0h， 生成 3-Amino-1,4-dioxy-7-trifluoromethoxy-quinoxaline-2-carbonitrile
  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
• 作为产物：
  描述：

  对三氟甲氧基苯胺 在 盐酸 、 sodium azide 、 硫酸 、 硝酸 、 sodium acetate 、 sodium nitrite 作用下， 以 溶剂黄146 为溶剂， 反应 1.42h， 生成 1-Azido-2-nitro-4-trifluoromethoxy-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

• Design and the synthesis of <scp>1‐heteroaryl</scp> ‐1,2,3‐triazoles connected to coumarins via ether linker
  作者：Muthipeedika Nibin Joy、Nikolai Beliaev、Tetyana V. Beryozkina、Vasiliy A. Bakulev

  DOI：10.1002/jhet.4025

  日期：2020.8

  In this paper, we report an efficient and versatile methodology for the synthesis of a series of novel heteroaryl‐1,2,3‐triazoles connected to 4‐methylcoumarin (4‐methyl‐2H‐chromen‐2‐one) via oxymethylene linker. The desired molecules were accessed by both two‐step synthesis and the one‐pot copper catalyzed cycloaddition reaction of heteroaromatic azides with coumarin containing acetylenes. The developed

  在本文中，我们报告了一种高效且通用的方法，用于合成一系列通过甲醛连接基连接到4-甲基香豆素（4-甲基-2H-铬-2--2-酮）的杂芳基-1,2,3-三唑。通过两步合成以及杂芳族叠氮化物与含有乙炔的香豆素的一锅铜催化的环加成反应，均可获得所需的分子。已发现开发的方案既容易又有效，可以以高收率制备一系列新型杂芳基-1,2,3-三唑-香豆素共轭物。成功地通过克级合成1,3-二甲基-6-（4-[（[[4-甲基-2-氧代-2H-铬--7-基]氧基]一锅法证实了一锅法的实用性甲基] -1H-1,1,2,3-三唑-1-基）嘧啶-2,4（1H，3H）-二酮。
• A facile access for the synthesis of 1-hetero(aryl)-1,2,3-triazoles linked to equol under mild conditions
  作者：Muthipeedika Nibin Joy、Nikolai Beliaev、Tetyana V. Beryozkina、Vasiliy A. Bakulev

  DOI：10.1080/00397911.2020.1792932

  日期：2020.10.17

  Abstract We herein report a convenient methodology for the synthesis of 1-hetero(aryl)-1,2,3-triazoles linked with equol by utilizing copper-catalyzed azide-alkyne cycloaddition reaction under exceptionally mild conditions. The salient features of this developed protocol include: easy isolation process, good to excellent yield of the products and appendage diversity of heteroaryl triazoles. Graphical

  摘要 我们在此报告了一种在极其温和的条件下利用铜催化的叠氮化物-炔环加成反应合成与雌马酚相连的 1-杂（芳基）-1,2,3-三唑的简便方法。该开发协议的显着特点包括：易于分离过程、产品的良好收率和杂芳基三唑的附属物多样性。图形概要
• 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.