6-trifluoromethyl-1,2,4-benzotriazin-3-amine 1-oxide | 494226-36-7

• 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: 6-trifluoromethyl-1,2,4-benzotriazin-3-amine 1-oxide
• 英文别名: 1-oxido-6-(trifluoromethyl)-1,2,4-benzotriazin-1-ium-3-amine
• CAS: 494226-36-7
• 化学式: C₈H₅F₃N₄O
• 分子量: 230.149
• InChiKey: ZWEAWMOQYBSUTP-UHFFFAOYSA-N

物化性质

• 沸点：
  411.2±55.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  77.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-trifluoromethyl-1,2,4-benzotriazin-3-amine 1-oxide 在 三氟乙酸 、 sodium nitrite 、 水 作用下， 反应 1.0h， 生成
  参考文献：
  名称：

  Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments

  摘要：

  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。

  公开号：

  EP1468688A2
• 作为产物：
  描述：

  3-氨基-4-硝基三氟甲苯 以29%的产率得到6-trifluoromethyl-1,2,4-benzotriazin-3-amine 1-oxide
  参考文献：
  名称：

  Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments

  摘要：

  本发明涉及一种协同作用的组合物，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。

  公开号：

  US20040192686A1

文献信息

• Structure−Activity Relationships of 1,2,4-Benzotriazine 1,4-Dioxides as Hypoxia-Selective Analogues of Tirapazamine
  作者：Michael P. Hay、Swarna A. Gamage、Mary S. Kovacs、Frederik B. Pruijn、Robert F. Anderson、Adam V. Patterson、William R. Wilson、J. Martin Brown、William A. Denny

  DOI：10.1021/jm020367+

  日期：2003.1.1

  well with that derived by the clonogenic endpoint. Most substituents, except 5- and 8-dimethylamino and 8-diethylamino, gave analogues less soluble than TPZ. E(1) values ranged from -240 mV through -670 mV (with TPZ having a value of -456 mV) and correlated well with the electronic parameter sigma for substituents at the 5-, 6-, 7-, and 8-positions. Aerobic cytotoxic potency showed a strong positive correlation

  替拉帕明（TPZ，1,2,4-苯并三嗪-3-胺1,4-二氧化物）是一种生物还原性低氧细胞毒素，目前在II / III期临床试验中结合放疗和基于顺铂的化学疗法。作为开发具有改善的溶解度/效能和治疗指数的TPZ类似物的程序的一部分，我们合成了34 1,2,4-苯并三嗪-3-胺1,4-二氧化物（BTO），以检查其结构活性关系（SAR）。环取代。系统地改变了5、6、7和8位上取代基的电子，疏水和空间参数，并确定了类似物的水溶性和单电子还原电位[E（1）] 。对于每种化合物，我们通过克隆形成存活率确定了有氧和低氧条件下小鼠SCCVII肿瘤细胞的体外杀伤作用，并确定了它们的相对低氧毒性（RHT；相对于TPZ）和低氧细胞毒性比（HCR）。使用96孔SRB增殖测定法独立评估了化合物的子集，其数据与克隆形成终点所得出的数据具有良好的相关性。除5-和8-二甲基氨基和8-二乙基氨基外，大多数取代基的溶解度均低于TPZ。E（1）值的范围是-240
• Radical properties governing the hypoxia-selective cytotoxicity of antitumor 3-amino-1,2,4-benzotriazine 1,4-dioxides
  作者：Robert F. Anderson、Sujata S. Shinde、Michael P. Hay、Swarna A. Gamage、William A. Denny

  DOI：10.1039/b502586a

  日期：——

  following the one-electron reduction of tirapazamine and its elimination of water from the initial reduction intermediate, and have suggested that this species is a cytotoxin. In this paper we have used pulse radiolysis to measure the one-electron reduction potentials of the benzotriazinyl radicals E(B*,H(+)/B) of 30 analogues of tirapazamine as well as the one-electron reduction potentials of their two-electron

  揭示抗癌药物替拉帕明（3-氨基-1,2,4-苯并三嗪1,4-二氧化物）引起缺氧选择性细胞毒性的自由基机制，被视为开发临床上有用的针对化学疗法的生物还原药物的方法。和耐辐射的缺氧肿瘤细胞。我们以前的研究指出，单电子还原替拉帕明并从初始的还原中间体中除去水后，会形成一个活性的苯并三嗪基自由基，并表明该物种是一种细胞毒素。在本文中，我们使用脉冲辐解法测量了替拉帕明的30个类似物的苯并三嗪基自由基E（B *，H（+）/ B）的单电子还原电势以及它们的两个电子还原的代谢物，苯并三嗪1氧化物E（B / B *-）。发现主要通过苯并三嗪1的单电子还原电位来追踪单电子还原的1,3-二氧化苯并三嗪1,4-二氧化物被氧反氧化的氧化还原依赖性，自由基的质子性和除水反应。 ，4-二氧化物E（A / A *-）。对已发表的SCCVII鼠肿瘤细胞系需氧和低氧克隆性细胞毒性数据进行多元回归分析，并在此研究中测量其物理化
• Oxidation of 2-Deoxyribose by Benzotriazinyl Radicals of Antitumor 3-Amino-1,2,4-benzotriazine 1,4-Dioxides
  作者：Sujata S. Shinde、Robert F. Anderson、Michael P. Hay、Swarna A. Gamage、William A. Denny

  DOI：10.1021/ja048740l

  日期：2004.6.1

  Tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide) is the lead bioreductive drug in clinical trials as an anticancer agent to kill refractory hypoxic cells of solid tumors. It has long been known that, upon metabolic one-electron reduction, tirapazamine induces lethal DNA double strand breaks in hypoxic cells. These strand breaks arise from radical damage to the ribose moiety of DNA, and in this pulse radiolysis and product analysis study we examine mechanistic aspects of the dual function of tirapazamine and analogues in producing radicals of sufficient power to oxidize 2-deoxyribose to form radicals, as well as the ability of the compounds to oxidize the resulting deoxyribose radicals to generate the strand breaks. Both the rate of oxidation of 2-deoxyribose and the radical yield increase with the one-electron reduction potentials of the putative benzotriazinyl radicals formed from the benzotriazine 1,4-dioxides. Subsequent oxidation of the 2-deoxyribose radicals by the benzotriazine 1,4-dioxides and 1-oxides proceeds through adduct formation followed by breakdown to form the radical anions of both species. The yield of the radical anions increases with increasing one-electron reduction potentials of the compounds. We have previously presented evidence that oxidizing benzotriazinyl radicals are formed following one-electron reduction of the benzotriazine 1,4-dioxides. The reactions reported in this work represent the kinetic basis of a short chain reaction leading to increased oxidation of 2-deoxyribose, a process which is dependent on the one-electron reduction potential of the benzotriazinyl radicals that are above a threshold value of ca. 1.24 V.
• 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。