N-phenyl-1,2,4-benzotriazin-3-amine 1-oxide | 121745-82-2

• 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: N-phenyl-1,2,4-benzotriazin-3-amine 1-oxide
• 英文别名: (1-oxy-benzo[e][1,2,4]triazin-3-yl)-phenyl-amine；1-oxido-N-phenyl-1,2,4-benzotriazin-1-ium-3-amine
• CAS: 121745-82-2
• 化学式: C₁₃H₁₀N₄O
• 分子量: 238.249
• InChiKey: HBKCCWGTHWGRMZ-UHFFFAOYSA-N

物化性质

• 熔点：
  197 °C
• 沸点：
  461.8±28.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-phenyl-1,2,4-benzotriazin-3-amine 1-oxide 在 双氧水 、 溶剂黄146 作用下， 以17.6%的产率得到1,2,4-Benzotriazin-3-amine, N-phenyl-, 1,4-dioxide
  参考文献：
  名称：

  3-Amino-1,2,4-benzotriazine-1,4-dioxide 衍生物的合成、结构和缺氧细胞毒性

  摘要：

  合成了一系列新型 3-氨基-1,2,4-苯并三嗪-1,4-二氧化物衍生物并筛选了它们对早幼粒细胞白血病HL-60、雄激素非依赖性前列腺肿瘤PC3、肝细胞癌Bel-7402的体外细胞毒性、人食道肿瘤 ECA-109 和人乳腺肿瘤 MCF-7 细胞系在缺氧和常氧条件下。大多数化合物在缺氧和常氧条件下都显示出更高的细胞毒活性。其中，与替拉扎明相比，化合物 61 和 62 显示出更有效的细胞毒活性和低氧选择性。

  DOI：

  10.1002/ardp.200600201
• 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 N-phenyl-1,2,4-benzotriazin-3-amine 1-oxide
  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。
• Arndt; Rosenau, Chemische Berichte, 1917, vol. 50, p. 1261
  作者：Arndt、Rosenau

  DOI：——

  日期：——
• Extravascular Transport of Drugs in Tumor Tissue:  Effect of Lipophilicity on Diffusion of Tirapazamine Analogues in Multicellular Layer Cultures
  作者：Frederik B. Pruijn、Joanna R. Sturman、H. D. Sarath Liyanage、Kevin O. Hicks、Michael P. Hay、William R. Wilson

  DOI：10.1021/jm049549p

  日期：2005.2.1

  The extravascular diffusion of antitumor agents is a key determinant of their therapeutic activity, but the relationships between physicochemical properties of drugs and their extravascular transport are poorly understood. It is well-known that drug lipophilicity plays an important role in transport across biological membranes, but the net effect of lipophilicity on transport through multiple layers of tumor cells is less clear. This study examines the influence of lipophilicity (measured as the octanol-water partition coefficient P) on the extravascular transport properties of the hypoxic cytotoxin tirapazamine (TPZ, 1) and a series of 13 neutral analogues, using multicellular layers (MCLs) of HT29 human colon carcinoma cells as an in vitro model for the extravascular compartment of tumors. Flux of drugs across MCLs was determined using diffusion chambers, with the concentration-time profile on both sides of the MCL measured by HPLC. Diffusion coefficients in the MCLs (D-MCL) were inversely proportional to M-r(0.5) (M-r, relative molecular weight), although this was a minor contributor to differences between compounds over the narrow M, range investigated. Differences in lipophilicity had a larger effect, with a sigmoidal dependence of DMCL on log P. Correcting for M, differences, lipophilic compounds (log P > 1.5) had ca. 15-fold higher DMCL than hydrophilic compounds (log P < -1). Using a pharmacokinetic/pharmacodynamic (PK/PD) model in which diffusion in the extravascular compartment of tumors is considered explicitly, we demonstrated that hypoxic cell kill is very sensitive to changes in extravascular diffusion coefficient of TPZ analogues within this range. This study shows that simple monosubstitution of TPZ can alter log P enough to markedly improve extravascular transport and activity against target cells, especially if rates of metabolic activation are also optimized.
• Synthesis and hypoxic–cytotoxic activity of some 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives
  作者：Faqin Jiang、Bo Yang、Lingling Fan、Qiaojun He、Yongzhou Hu

  DOI：10.1016/j.bmcl.2006.05.095

  日期：2006.8

  A series of 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives 1 have been synthesized and evaluated for their cytotoxic activity in vitro against human leukemia cell lines: Molt-4, K562, HL60, human liver cancer cell Hep-G2, human prostate cancer cell PC-3 in hypoxia. Most of the compounds showed more potent activity than TPZ. Compounds 1i and 1m displayed encouraging superior activity against Molt-4

  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。
• Synthesis, Structure and Hypoxic Cytotoxicity of 3-Amino-1,2,4-benzotriazine-1,4-dioxide Derivatives
  作者：Faqin Jiang、Qinjie Weng、Rong Sheng、Qing Xia、Qiaojun He、Bo Yang、Yongzhou Hu

  DOI：10.1002/ardp.200600201

  日期：2007.5

  3‐amino‐1,2,4‐benzotriazine‐1,4‐dioxide derivatives were synthesized and screened for their in vitro cytotoxicity against promyelocytic leukemia HL‐60, androgen‐independent prostate tumor PC3, hepatocellular carcinoma Bel‐7402, human esophagus tumor ECA‐109, and human breast tumor MCF‐7 cell lines in hypoxia and in normoxia. Most compounds showed higher cytotoxic activity both in hypoxia and in normoxia

  合成了一系列新型 3-氨基-1,2,4-苯并三嗪-1,4-二氧化物衍生物并筛选了它们对早幼粒细胞白血病HL-60、雄激素非依赖性前列腺肿瘤PC3、肝细胞癌Bel-7402的体外细胞毒性、人食道肿瘤 ECA-109 和人乳腺肿瘤 MCF-7 细胞系在缺氧和常氧条件下。大多数化合物在缺氧和常氧条件下都显示出更高的细胞毒活性。其中，与替拉扎明相比，化合物 61 和 62 显示出更有效的细胞毒活性和低氧选择性。