1,6-二硝基芘 | 42397-64-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 中文名称: 1,6-二硝基芘
• 中文别名: 1，6-二硝基芘
• 英文名称: 1,6-dinitropyrene
• CAS: 42397-64-8
• 化学式: C₁₆H₈N₂O₄
• mdl: MFCD00010494
• 分子量: 292.251
• InChiKey: GUXACCKTQWVTLG-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C(lit.)
• 沸点：
  434.19°C (rough estimate)
• 密度：
  1.2855 (rough estimate)
• 颜色/状态：
  Light-brown needles, recrystallized from benzene and methanol
• 溶解度：
  In water, 5.4X10-3 mg/L at 25 °C (est)
• 蒸汽压力：
  9.1X10-10 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxide/.
• 保留指数：
  478.51
• 稳定性/保质期：
  常规情况下不会分解，也没有危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  91.6
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

在氩气气氛下，大鼠和狗的肝脏细胞质��化了1,6-二硝基芘还原为1-氨基-6-硝基芘和1,6-二氨基芘...还检测到了1-乙酰氨基-6-硝基芘作为代谢物...

Under argon atmosphere, rat and dog liver cytosol catalyzed the reduction of 1,6-dinitropyrene to 1-amino-6-nitropyrene and 1,6-diaminopyrene ... 1-acetylamino-6-nitropyrene was also detected as a metabolite ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

这项研究旨在监测连续细胞系的N-乙酰转移酶活性，这些细胞系对硝基芳烃化合物的毒性作用敏感性不同。转移酶活性是针对磺胺二甲嘧啶和对氨基苯甲酸这些乙酰受体在部分纯化的细胞溶质制剂中测量的。例如，对1,6-二硝基芘（1,6-DNP）敏感的细胞系，如仓鼠V79、BHK、大鼠肝癌H4IIEC3G-或成纤维细胞208F，具有较高的转移酶活性，范围在120-270 nmol/min x mg蛋白质。相比之下，对1,6-DNP有抗性的人肺细胞NCI-H322、小鼠和大鼠肝癌细胞BW1J和H5，分别含有很少或低转移酶活性，小于15 nmol/min x mg。在某些细胞系中，如大鼠肝癌HTC、2sFou和5L，表达中等转移酶活性，范围在25-50 nmol/min x mg蛋白质，1,6-DNP的敏感性与乙酰转移酶水平之间没有明显的相关性。结果表明，乙酰化是在哺乳动物细胞中将1,6-DNP激活为有毒产物的关键步骤。

This study was aimed at monitoring N-acetyltransferase activities of continuous cell lines, which differ in their sensitivity to the toxic effects of nitroaromatic compounds. Transferase activities were measured toward the acetyl acceptors sulfamethazine and p-aminobenzoic acid in partially purified preparation of cytosols. Cell lines such as hamster V79, BHK, rat hepatoma H4IIEC3G- or fibroblast 208F, which are sensitive to 1,6-dinitropyrene (1,6-DNP), possess high transferase activities ranging from 120-270 nmol/min x mg protein. In contrast, human lung cells NCI-H322, mouse and rat hepatoma cells BW1J and H5, respectively, which are resistant to 1,6-DNP contain no or low transferase activity of less than 15 nmol/min x mg. There was no apparent correlation between 1,6-DNP sensitivity and acetyltransferase levels in a few cell lines, e.g. rat hepatoma HTC, 2sFou and 5L, which express intermediate transferase activities ranging from 25-50 nmol/min x mg protein. The results suggest that acetylation is an essential step in activating 1,6-DNP to toxic products in mammalian cells.

来源:Hazardous Substances Data Bank (HSDB)

代谢

二硝基芘是具有诱变性的环境污染物。在这些化合物中，1,6-二硝基芘是一种强致癌物，而1,3-二硝基芘似乎只具有弱或非致癌性。二硝基芘的两电子还原产生硝基-亚硝基芘，这些物质之前已被证实是这些化合物在体外的主要有氧代谢物。进一步还原亚硝基芘是将其激活为与DNA反应的N-羟基胺所必需的。在这项工作中，合成了1-硝基-3-亚硝基芘，并比较了1-硝基-3-亚硝基芘与1-硝基-6-亚硝基芘的电化学和酶催化还原。通过循环伏安法确定，1-硝基-3-亚硝基芘、1-硝基-6-亚硝基芘及其母体二硝基芘的还原电位相似，尽管1-硝基-3-亚硝基芘的阴极峰电位比其他三种化合物稍微更负。与1-硝基-3-亚硝基芘相比，1-硝基-6-亚硝基芘还原为能还原琥珀酰化细胞色素c的中间体的NADPH介导还原更快。在大鼠肝微粒体或细胞质存在的情况下，1-硝基-6-亚硝基芘的还原速度比1-硝基-3-亚硝基芘快。这些硝基-亚硝基芘还原速率的差异可能是1,3-二硝基芘相对于1,6-二硝基芘具有较低致癌潜力的一个因素。

Dinitropyrenes are mutagenic environmental pollutants. Of these compounds, 1,6-dinitropyrene is a potent tumorigen while 1,3-dinitropyrene appears to be weakly or non-tumorigenic. Two-electron reduction of dinitropyrenes yields nitro-nitrosopyrenes, which have been shown previously to be the major aerobic metabolites of these compounds in vitro. Further reduction of nitrosopyrenes is required for their activation to a DNA-reactive N-hydroxylamines. In this work, 1-nitro-3-nitrosopyrene was synthesized and the electrochemical and enzyme-catalyzed reduction of 1-nitro-3-nitrosopyrene has been compared with that of 1-nitro-6-nitrosopyrene. As determined by cyclic voltammetry, the reduction potentials of 1-nitro-3-nitrosopyrene, 1-nitro-6-nitrosopyrene and their parent dinitropyrenes were similar, although 1-nitro-3-nitrosopyrene did have a slightly more negative cathodic peak potential than the other three compounds. The NADPH-mediated reduction of 1-nitro-6-nitrosopyrene to intermediates which reduce succinoylated cytochrome c was faster than that of 1-nitro-3-nitrosopyrene. In the presence of rat liver microsomes or cytosol, the reduction of 1-nitro-6-nitrosopyrene was faster than that of 1-nitro-3-nitrosopyrene. These differences in the rates of nitro-nitrosopyrene reduction may be one factor contributing to the lower tumorigenic potential of 1,3-dinitropyrene relative to 1,6-dinitropyrene.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠乳腺细胞质中，与1,6-二硝基芘在无氧条件下孵育时，检出了1-硝基-6-硝基芘、1-氨基-6-硝基芘和1,6-二氨基芘作为代谢产物。

1-Nitro-6-nitrosopyrene, 1-amino-6-nitropyrene and 1,6-diaminopyrene were detected as metabolites in rat mammary gland cytosol incubated with 1,6-dinitropyrene under anaerobic conditions.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

1,6-二硝基芘在实验动物中具有充分的致癌性证据。目前没有来自人类研究中关于1,6-二硝基芘致癌性的数据。总体评估：1,6-二硝基芘可能对人类致癌（2B组）。

There is sufficient evidence for the carcinogenicity in experimental animals of 1,6-dinitropyrene. No data were available from studies in humans on the carcinogenicity of 1,6-dinitropyrene. Overall evaluation: 1,6-Dinitropyrene is possibly carcinogenic to humans (Group 2B).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

1,6-二硝基芘根据充分的证据被合理预期为人类致癌物，该证据显示在多种实验动物中通过多种暴露途径在多个部位形成恶性肿瘤。

1,6-Dinitropyrene is reasonably anticipated to be a human carcinogen based on sufficient evidence of malignant tumor formation in multiple species of experimental animals, at multiple sites and by multiple routes of exposure.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：1,6-二硝基芘

IARC Carcinogenic Agent:1,6-Dinitropyrene

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第46卷：（1989年）柴油和汽油发动机排气及一些硝基芳烃

IARC Monographs:Volume 46: (1989) Diesel and Gasoline Engine Exhausts and Some Nitroarenes

来源:International Agency for Research on Cancer (IARC)

安全信息

• 危险品标志：
  T
• 危险类别码：
  R45
• 海关编码：
  2904209090

反应信息

• 作为反应物：
  描述：

  1,6-二硝基芘 在 乙醇 、 镍 作用下， 生成 1,6-二氨基芘
  参考文献：
  名称：

  Vollmann et al., Justus Liebigs Annalen der Chemie, 1937, vol. 531, p. 1,121

  摘要：

  DOI：
• 作为产物：
  描述：

  芘 在 硝酸 作用下， 生成 1,6-二硝基芘
  参考文献：
  名称：

  Photoinduced electron-transfer systems consisting of electron-donating pyrenes or anthracenes and benzimidazolines for reductive transformation of carbonyl compounds

  摘要：

  Photoinduced electron-transfer reactions of several ketone substrates were studied to evaluate the utilities of 1,6-bis(dimethyl-amino)pyrene (BDMAP), 1,6-dimethoxypyrene (DMP), 9,10-bis(dimethlylamino)anthracene (BDMAA), and 9,10-dimethoxyanthracene (DMA) as electron-donating sensitizers cooperating with 2-aryl-13-dimethylbenzimidazolines. BDMAP and DMP generally led higher conversion of ketones and better yield of reduction products compared to BDMAA and DMA. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.03.061

文献信息

• IRON OXIDE SUPPORTED RHODIUM CATALYST FOR NITROARENE REDUCTION
  申请人：King Fahd University of Petroleum and Minerals

  公开号：US20200298212A1

  公开（公告）日：2020-09-24

  A supported catalyst having rhodium particles with an average diameter of less than 1 nm disposed on a support material containing magnetic iron oxide (e.g. Fe 3 O 4 ). A method of producing the supported catalyst and a process of reducing nitroarenes to corresponding aromatic amines employing the supported catalyst with a high product yield are also described. The supported catalyst may be recovered with ease using an external magnet and reused.

  一个支撑的催化剂，其上分布有平均直径小于1纳米的铑颗粒，载体材料含有磁性氧化铁（例如Fe3O4）。还描述了生产该支撑催化剂的方法以及使用该支撑催化剂将硝基芳烃还原为相应芳香胺的过程，该过程具有高产品收率。可以使用外部磁铁轻松回收支撑催化剂，并重复使用。
• Diaminopyrene modified reduced graphene oxide as a novel electrode material for excellent performance supercapacitors
  作者：Hongwei Kang、Chengpeng Zhang、Yonggui Xu、Weiyang Zhang、Jianhua Jiao、Zhikun Li、LeiLei Zhu、Xiaoqian Liu

  DOI：10.1039/c9ra10429a

  日期：——

  Schematic illustration of the facile synthesis process of DAPrGOs nanocomposites, Ragone plots and the superior cyclic stability of the assembled DAPrGO1//DAPrGO1 SSS.

  DAPrGOs纳米复合材料的简易合成过程示意图，Ragone图和组装的DAPrGO1//DAPrGO1 SSS的优越循环稳定性。
• Compounds, compositions and methods for the treatment of viral infections and other medical disorders
  申请人：Almond R. Merrick

  公开号：US20070003608A1

  公开（公告）日：2007-01-04

  The present application provides methods and compositions for improving the bioavailability of a lipid-containing antiviral compound, and in particular, an antiviral lipid-containing compound. In one embodiment, pharmaceutically acceptable compositions are provided that include an antiviral lipid-containing compound, or salt, ester, or prodrug thereof and one or more bioavailability enhancing compounds, such as inhibitors of cytochrome P450 enzymes.

  本申请提供了一种提高含脂质抗病毒化合物的生物利用度的方法和组合物，尤其是一种含脂质抗病毒化合物。在一种实施例中，提供了药学上可接受的组合物，其中包括一种含脂质抗病毒化合物或其盐、酯或前药，以及一种或多种生物利用度增强化合物，例如细胞色素P450酶抑制剂。
• COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS AND OTHER MEDICAL DISORDERS
  申请人：Almond Merrick R.

  公开号：US20110015149A1

  公开（公告）日：2011-01-20

  The present application provides methods and compositions for improving the bioavailability of a lipid-containing antiviral compound, and in particular, an antiviral lipid-containing compound. In one embodiment, pharmaceutically acceptable compositions are provided that include an antiviral lipid-containing compound, or salt, ester, or prodrug thereof and one or more bioavailability enhancing compounds, such as inhibitors of cytochrome P450 enzymes.

  本申请提供了一种改善含脂质抗病毒化合物的生物利用度的方法和组合物，特别是一种含脂质抗病毒化合物。在一种实施方式中，提供了药学上可接受的组合物，包括一种含脂质抗病毒化合物或其盐、酯或前药，以及一种或多种生物利用度增强化合物，例如细胞色素P450酶抑制剂。
• Method for increasing bioavailability of oral pharmaceutical compositions
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP1127579A2

  公开（公告）日：2001-08-29

  A method for increasing bioavailability of an orally administered hydrophobic pharmaceutical compound, which comprises orally administering the pharmaceutical compound to a mammal in need of treatment with the compound concurrently with a bioenhancer comprising an inhibitor of a cytochrome P450 3A enzyme or an inhibitor of P-glycoprotein-mediated membrane transport, the bioenhancer being present in sufficient amount to provide bioavailability of the compound in the presence of the bioenhancer greater than the bioavailability of the compound in the absence of the bioenhancer.

  一种提高口服疏水性药物化合物生物利用度的方法，包括向需要用该化合物治疗的哺乳动物口服该药物化合物，同时口服一种生物增强剂，该生物增强剂包括细胞色素 P450 3A 酶抑制剂或 P 糖蛋白介导的膜转运抑制剂，生物增强剂的存在量足以使存在生物增强剂时的化合物生物利用度大于不存在生物增强剂时的化合物生物利用度。

表征谱图