2-[(1-oxido-1,2,4-benzotriazin-3-yl)amino]ethanol | 54215-05-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 2-[(1-oxido-1,2,4-benzotriazin-3-yl)amino]ethanol
• 英文别名: 2-(1-oxy-benzo[1,2,4]triazin-3-ylamino)-ethanol；2-(1-oxy-benzo[e][1,2,4]triazin-3-ylamino)-ethanol；2-(1-Oxy-benzo[e][1,2,4]triazin-3-ylamino)-aethanol；3-(2-hydroxyethylamino)-1,2,4-benzotriazine 1-oxide；2-[(1-oxido-1,2,4-benzotriazin-1-ium-3-yl)amino]ethanol
• CAS: 54215-05-3
• 化学式: C₉H₁₀N₄O₂
• 分子量: 206.204
• InChiKey: XWODDDOGTNZZGI-UHFFFAOYSA-N

物化性质

• 熔点：
  214-218 °C(Solv: methanol (67-56-1); dichloromethane (75-09-2))
• 沸点：
  459.6±47.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(1-oxido-1,2,4-benzotriazin-3-yl)amino]ethanol 在 双氧水 、 溶剂黄146 作用下， 反应 24.0h， 生成 3-(2-hydroxyethylamino)-1,2,4-benzotriazine 1,4-dioxide
  参考文献：
  名称：

  某些3-氨基-1,2,4-苯并三嗪-1,4-二氧化物衍生物的合成和低氧细胞毒活性。

  摘要：

  合成了一系列3-氨基-1,2,4-苯并三嗪-1,4-二氧化物衍生物1并评估了其对人白血病细胞系Molt-4，K562，HL60，人肝癌的体外细胞毒活性细胞Hep-G2，缺氧的人前列腺癌细胞PC-3。大多数化合物显示出比TPZ更强的活性。化合物1i和1m对Molt-4和HL-60细胞系显示出令人鼓舞的优异活性。三种潜在的衍生物接受了针对Molt-4和HL-60细胞系的低氧和常氧活性测试，并显示出明显的低氧选择性。进一步的机理研究表明，化合物1i和1k在Molt-4细胞中的细胞毒活性可能是通过调节p53蛋白表达和线粒体膜电位（DeltaPsi（m））来介导的。

  DOI：

  10.1016/j.bmcl.2006.05.095
• 作为产物：
  描述：

  异腈酸2-硝基苯 在 sodium hydroxide 、 氨 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 12.5h， 生成 2-[(1-oxido-1,2,4-benzotriazin-3-yl)amino]ethanol
  参考文献：
  名称：

  某些3-氨基-1,2,4-苯并三嗪-1,4-二氧化物衍生物的合成和低氧细胞毒活性。

  摘要：

  合成了一系列3-氨基-1,2,4-苯并三嗪-1,4-二氧化物衍生物1并评估了其对人白血病细胞系Molt-4，K562，HL60，人肝癌的体外细胞毒活性细胞Hep-G2，缺氧的人前列腺癌细胞PC-3。大多数化合物显示出比TPZ更强的活性。化合物1i和1m对Molt-4和HL-60细胞系显示出令人鼓舞的优异活性。三种潜在的衍生物接受了针对Molt-4和HL-60细胞系的低氧和常氧活性测试，并显示出明显的低氧选择性。进一步的机理研究表明，化合物1i和1k在Molt-4细胞中的细胞毒活性可能是通过调节p53蛋白表达和线粒体膜电位（DeltaPsi（m））来介导的。

  DOI：

  10.1016/j.bmcl.2006.05.095

文献信息

• Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments
  申请人：Auckland Uniservices Limited

  公开号：EP1468688A2

  公开（公告）日：2004-10-20

  The present invention relates to a synergetistic composition comprising one or more benzoazine-mono-N-oxides, and one or more benzoazine 1,4 dioxides for use in cancer therapy. The invention also provides a range of novel 1,2,4 benzoazine-mono-N-oxides and related analogues. These can be used as potentiators of the cytotoxicity of existing anticancer drugs and therapies for cancer treatment.

  本发明涉及一种协同组合物，包括一种或多种苯并噁唑-单-N-氧化物，以及一种或多种苯并噁唑1,4-二氧化物，用于癌症治疗。 该发明还提供了一系列新颖的1,2,4苯并噁唑-单-N-氧化物及相关类似物。这些可以用作增强现有抗癌药物的细胞毒性和癌症治疗的治疗剂。
• 1, 2, 4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents
  申请人：Lee W. William

  公开号：US20050153961A1

  公开（公告）日：2005-07-14

  A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.

  本发明揭示了一种使用1,2,4-苯并三氮唑氧化物的方法，其中一些是新型化合物，作为放射增敏剂和选择性细胞毒剂。这些化合物被证明能够特异性地增敏缺氧肿瘤细胞。其中一些还被披露为这些细胞的特异性细胞毒剂。此外，它们还表现出在药物与细胞进行缺氧孵育之前或之后，对有氧细胞具有意外的增敏能力。这为与正常细胞相比选择性增敏肿瘤提供了基础。本发明还揭示了一种制备1,2,4-苯并三氮唑氧化物的新方法。
• 1,2,4-Benzotriazine oxides as radiosensitizers and selective cytotoxic agents
  申请人：——

  公开号：US20020103200A1

  公开（公告）日：2002-08-01

  A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.

  本发明公开了使用1,2,4-苯并三氮唑氧化物的方法，其中一些是新化合物，作为放射增敏剂和选择性细胞毒剂。这些化合物被证明能够特异性地增敏缺氧肿瘤细胞。其中一些还被证明可用作这些细胞的特异性细胞毒剂。此外，它们还表现出一种意外的能力，在药物与细胞进行缺氧孵育之前或之后，增敏有氧细胞。这为与正常细胞相比选择性增敏肿瘤提供了基础。本发明还公开了制备1,2,4-苯并三氮唑氧化物的新方法。
• Pharmacokinetic/Pharmacodynamic Model-Guided Identification of Hypoxia-Selective 1,2,4-Benzotriazine 1,4-Dioxides with Antitumor Activity: The Role of Extravascular Transport
  作者：Michael P. Hay、Kevin O. Hicks、Frederik B. Pruijn、Karin Pchalek、Bronwyn G. Siim、William R. Wilson、William A. Denny

  DOI：10.1021/jm070670g

  日期：2007.12.13

  Pharmacokinetic/pharmacodynamic (PK/PD) modeling has shown the antitumor activity of tirapazamine (TPZ), a bioreductive hypoxia-selective cytotoxin, to be limited by poor penetration through hypoxic tumor tissue. We have prepared a series of 1,2,4-benzotriazine 1,4-dioxide (BTO) analogues of TPZ to improve activity against hypoxic cells by increasing extravascular transport. The 6 substituents modified lipophilicity and rates of hypoxic metabolism. 3-Alkylamino substituents increased aqueous solubility and also influenced lipophilicity and hypoxic metabolism. PK/PD model-guided screening was used to select six BTOs for evaluation against hypoxic cells in HT29 human tumor xenografts. All six BTOs were active in vivo, and two provided greater hypoxic cell killing than TPZ because of improved transport and/or plasma PK. This PK/PD model considers two causes of therapeutic failure (limited tumor penetration and poor plasma pharmacokinetics) often not addressed early in drug development and provides a general strategy for selecting candidates for in vivo evaluation during lead optimization.
• 1,2,4-BENZOTRIAZINE OXIDES AS RADIOSENSITIZERS AND SELECTIVE CYTOTOXIC AGENTS
  申请人：SRI INTERNATIONAL

  公开号：EP0413706A1

  公开（公告）日：1991-02-27