4-(6-hydroxyhexylamino)-7-nitro-2,1,3-benzoxadiazole | 627546-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶二唑类
• 英文名称: 4-(6-hydroxyhexylamino)-7-nitro-2,1,3-benzoxadiazole
• 英文别名: 7-(6-hydroxyhexyl)amino-4-nitro-2,1,3-benzoxadiazole；6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)hexan-1-ol；6-((7-nitrobenzo-1,2,5-oxadiazol-4-yl)amino)hexan-1-ol；NBDNHEX；6-[(4-Nitro-2,1,3-benzoxadiazol-7-yl)amino]hexan-1-ol
• CAS: 627546-71-8
• 化学式: C₁₂H₁₆N₄O₄
• 分子量: 280.283
• InChiKey: DWMPVGIIXUFRDI-UHFFFAOYSA-N

物化性质

• 熔点：
  99.0-100.5 °C
• 沸点：
  501.7±60.0 °C(Predicted)
• 密度：
  1.373±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(6-hydroxyhexylamino)-7-nitro-2,1,3-benzoxadiazole 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.17h， 生成 6-(methyl(7-nitrobenzo-1,2,5-oxadiazol-4-yl)amino)hexyl methanesulfonate
  参考文献：
  名称：

  一种用于脂质双层的新型荧光溶剂化变色探针

  摘要：

  摘要 细胞膜是一个主要由脂质和蛋白质构成的异质系统，其物理状态受到精细调节以保证正常功能。在膜研究中使用的众多分析技术中，一个特殊的角色是荧光显微镜。荧光显微镜可以对模型膜和活体样品进行快速、无中断的研究。许多荧光探针是已知的，但它们中的大多数不适用于膜研究，因为它们要么改变膜结构，要么在细胞中内化。在这项工作中，我们报告了一种新型荧光膜探针的合理设计和合成及其在模型膜中的表征。该探针由 7-nitrobenz-2-oxa-1 的荧光芳香核组成，3-二唑 (NBD) 在光谱的可见光区域发射。荧光团与两性离子结构和 18 个碳原子的饱和链相连，以防止细胞内化并选择性地将其固定在外膜层上。值得注意的是，该探针显示出一定程度的溶剂化变色，这一特征可用于评估生物膜的液体有序和液体无序组成。

  DOI：

  10.1080/10610278.2017.1372583
• 作为产物：
  描述：

  6-氨基-1-己醇 、 4-氯-7-硝基苯并-2-氧杂-1,3-二唑 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 4-(6-hydroxyhexylamino)-7-nitro-2,1,3-benzoxadiazole
  参考文献：
  名称：

  用于半胱氨酸选择性蛋白质标记和二硫键重桥的二乙炔基次膦酸盐

  摘要：

  二乙炔基次膦酸盐被开发为双功能亲电子试剂，用于肽、蛋白质和抗体的位点选择性修饰。它们的一个缺电子三键选择性地与硫醇反应，并定位亲电子部分，以便随后与另一个硫醇进行分子内或分子间反应。发现所获得的缀合物在人血浆中和存在小硫醇的情况下是稳定的。我们进一步证明该方法适用于生成用于细胞内递送的功能性蛋白质缀合物。最后，该试剂类用于生成功能性均质重桥抗体，这些抗体对其靶标保持特异性。其模块化合成、硫醇选择性和缀合物稳定性使二乙炔基次膦酸盐成为生物和制药应用中蛋白质缀合的理想候选者。

  DOI：

  10.1002/anie.202100683

文献信息

• Fluorescent Molecular Thermometers Based on Polymers Showing Temperature-Induced Phase Transitions and Labeled with Polarity-Responsive Benzofurazans
  作者：Seiichi Uchiyama、Yuriko Matsumura、A. Prasanna de Silva、Kaoru Iwai

  DOI：10.1021/ac0346914

  日期：2003.11.1

  Poly(N-isopropylacrylamide) in aqueous solution undergoes a phase transition at ∼32 °C. The fluorescence properties of benzofurazans are affected by solvent polarity. We combine these two characteristics for the first time to develop sensitive fluorescent molecular thermometers. Five fluorescent monomers having a benzofurazan skeleton were synthesized, and the copolymers of N-isopropylacrylamide (NIPAM) and a small quantity of the fluorescent monomer were obtained to investigate their fluorescence properties. With increase in temperature, the copolymers in water showed the temperature-induced phase transition at ∼32 °C and the fluorescence intensities of the copolymers concurrently increased. Especially, for the copolymer of 4-N-(2-acryloyloxyethyl)-N-methylamino-7-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole and NIPAM, the fluorescence intensity at 37 °C was 13.3-fold that seen at 29 °C. The sensitive range of temperature of these fluorescent molecular thermometers is changed by the replacement of the NIPAM units by N-isopropylmethacrylamide or N-n-propylacrylamide units in the copolymers. The basis of these fluorescent molecular thermometers is the decrease in the microenvironmental polarities near the main chains of the copolymers with increasing temperature, as confirmed from the maximum emission wavelengths of the benzofurazan units in the copolymers. The responses from the copolymers to the change in temperature are reversible and exactly repeatable during at least 10 cycles of heating and cooling.

  水溶液中的聚（N-异丙基丙烯酰胺）在 ∼32 °C 时发生相变。苯并呋喃的荧光特性受溶剂极性的影响。我们首次将这两种特性结合起来，开发出了灵敏的荧光分子温度计。我们合成了五种以苯并呋喃为骨架的荧光单体，并得到了 N-异丙基丙烯酰胺（NIPAM）与少量荧光单体的共聚物，以研究它们的荧光特性。随着温度的升高，水中的共聚物在 ∼32 °C处出现了温度诱导的相变，共聚物的荧光强度也随之增加。特别是 4-N-（2-丙烯酰氧乙基）-N-甲基氨基-7-N,N-二甲基氨基磺酰基-2,1,3-苯并噁二唑和 NIPAM 的共聚物，在 37 °C 时的荧光强度是 29 °C 时的 13.3 倍。将共聚物中的 NIPAM 单元替换为 N-异丙基甲基丙烯酰胺或 N-正丙基丙烯酰胺单元，可改变这些荧光分子温度计的灵敏温度范围。这些荧光分子温度计的基础是共聚物主链附近的微环境极性随着温度的升高而降低，共聚物中苯并呋喃单元的最大发射波长证实了这一点。共聚物对温度变化的反应是可逆的，在至少 10 个加热和冷却周期中都可以准确重复。
• [EN] USE OF 7-NITRO-2,1,3 BENZOXADIAZOLE DERIVATIVES FOR ANTICANCER THERAPY<br/>[FR] UTILISATION DE DERIVES DE 7-NITRO-2,1,3 BENZOXADIAZOLE A DES FINS DE THERAPIE ANTICANCEREUSE
  申请人：UNIV ROMA

  公开号：WO2004093874A1

  公开（公告）日：2004-11-04

  Derivatives of the heterocyclic compound known as 7-nitro-benzofurazan or 7-nitro-2,1,3-benzoxadiazole, of the general formula (I) are proposed as agents having a strong inhibiting activity towards members of the glutathione S-transferase (GST) superfamily that are hyperexpressed in cancer cells, and make them particularly resistant to many stress factors. These compounds are useful in the production of pharmaceutical drugs to be used in anticancer therapy, and may be employed either alone or in combination with other chemotherapeutic agents. The invention also concerns preparations for anticancer treatment that also include as active ingredient at least one of the derivatives of formula (I), optionally in combination with other chemotherapeutic agents.

  本发明提出了一种杂环化合物7-硝基苯并呋喃或7-硝基-2,1,3-苯并噻二唑的衍生物，其通式为(I)，作为一种具有强烈抑制谷胱甘肽S转移酶（GST）超家族成员的活性剂，这些成员在癌细胞中高表达，并使它们对许多应激因素特别具有抵抗力。这些化合物在制备抗癌药物方面非常有用，可以单独使用或与其他化疗药物联合使用。本发明还涉及抗癌治疗的制剂，其活性成分包括至少一种通式(I)的衍生物，可选地与其他化疗药物联合使用。
• Use of 7-nitro-2,1,3 benzoxadiazole derivatives for anticancer therapy
  申请人：Caccuri Maria Anna

  公开号：US20060247284A1

  公开（公告）日：2006-11-02

  Derivatives of the heterocyclic compound known as 7-nitro-benzofurazan or 7-nitro-2,1,3-benzoxadiazole, are agents having a strong inhibiting activity towards members of the glutathione S-transferase (GST) superfamily that are hyperexpressed in cancer cells, and make them particularly resistant to many stress factors. These compounds are useful in the production of pharmaceutical drugs to be used in anticancer therapy, and may be employed either alone or in combination with other chemotherapeutic agents.

  7-硝基苯并呋喃或7-硝基-2,1,3-苯并噻二唑这种杂环化合物的衍生物，是一种对谷胱甘肽S-转移酶（GST）超家族成员具有强烈抑制活性的代理物，在癌细胞中高表达，并使它们特别耐受许多压力因素。这些化合物在制备用于抗癌治疗的药物方面非常有用，可以单独使用或与其他化疗药物联合使用。
• Synthesis and structure–activity relationship of new cytotoxic agents targeting human glutathione-S-transferases
  作者：Dante Rotili、Anastasia De Luca、Domenico Tarantino、Silvia Pezzola、Mariantonietta Forgione、Blasco Morozzo della Rocca、Mattia Falconi、Antonello Mai、Anna Maria Caccuri

  DOI：10.1016/j.ejmech.2014.10.033

  日期：2015.1

  The 6((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX, 1), a "suicide inhibitor" of the glutathione-S-transferase GSTP1-1, showed pro-apoptotic properties in tumor cells, but in vivo studies were limited by poor bioavailability and high affinity towards GSTM2-2, expressed in many non-cancerous tissues. Here we describe the synthesis and biological characterization of new 1 analogs (2-40), in which the hydroxyhexyl portion at the C4-sulfur atom has been replaced with phenyl-containing moieties as well as substituted alkyl chains. Some of the new compounds displayed 10-100 times increased water-solubility (8, 11, 17, 26-28, 34, 35), and most of them showed higher GSTP1-1 selectivity (2-20, 23-26, 31-33, 35) than 1. The presence of a phenyl ring with polar substituents is in general associated, with some exceptions (23, 24) to low cytotoxicity in osteosarcoma U-2OS cells. Differently, some alkyl derivatives possess cytotoxicity comparable (26, 34,35) or higher (30, 32) than 1. Among the novel compounds, selected ones (26, 27, 34, and 35) deserve further investigation for their anticancer potential. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis of novel fluorescently labeled sphingomyelin derivatives useful for sphingomyelinase assay
  作者：John J. Gaudino、Kirsten Bjergarde、Po-Ying Chan-Hui、Clifford D. Wright、David S. Thomson

  DOI：10.1016/s0960-894x(97)00184-4

  日期：1997.5

  Substrates for the sphingomyelinase enzyme class have been prepared, which contain a fluorescent tag and a biotin moiety. These molecules are useful for development of rapid high throughput assays for sphingomyelinase activity. It was observed that retaining the choline ammonium group (as found in the native sphingomyelinase substrate) in synthetic substrates was critical to retain high cleavage rate by the enzyme. (C) 1997 Elsevier Science Ltd.