7-chloro-1,2,4-benzotriazin-3-amine 1-oxide | 18671-92-6

• 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: 7-chloro-1,2,4-benzotriazin-3-amine 1-oxide
• 英文别名: 7-chloro-1-oxido-1,2,4-benzotriazin-1-ium-3-amine；3-amino-7-chloro-1,2,4-benzotriazine 1-oxide；7-chloro-1-oxy-benzo[1,2,4]triazin-3-ylamine；7-chloro-1-oxy-benzo[e][1,2,4]triazin-3-ylamine；7-Chlor-1-oxy-benzo[e][1,2,4]triazin-3-ylamin；3-Amino-7-chloro-1,2,4-benzotriazine-1-oxide
• CAS: 18671-92-6
• 化学式: C₇H₅ClN₄O
• mdl: MFCD00024040
• 分子量: 196.596
• InChiKey: OXILOAZZXVNKSG-UHFFFAOYSA-N

物化性质

• 熔点：
  302 °C (decomp)
• 沸点：
  462.4±37.0 °C(Predicted)
• 密度：
  1.75±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933699090

反应信息

• 作为反应物：
  描述：

  7-chloro-1,2,4-benzotriazin-3-amine 1-oxide 在 溶剂黄146 作用下， 反应 4.0h， 以50%的产率得到败脂酸,丙-2-烯腈,苯乙烯
  参考文献：
  名称：

  1,2,4-苯并三嗪1,4-二氧化物作为替拉帕明的低氧选择性类似物的构效关系。

  摘要：

  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

  DOI：

  10.1021/jm020367+
• 作为产物：
  描述：

  N-(4-氯-2-硝基苯基)乙酰胺 在 盐酸 作用下， 以 乙醚 、 水 为溶剂， 反应 7.0h， 生成 7-chloro-1,2,4-benzotriazin-3-amine 1-oxide
  参考文献：
  名称：

  Discovery and Optimization of Benzotriazine Di-N-Oxides Targeting Replicating and Nonreplicating Mycobacterium tuberculosis

  摘要：

  Compounds bactericidal against both replicating and nonreplicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-N-oxides (BTOs) are potently bactericidal against replicating and nonreplicating Mtb. Medicinal chemistry optimization, guided by semiempirical molecular orbital calculations, identified a new lead compound (20q) from this series with an MIC of 0.31 mu g/mL against H37Rv and a cytotoxicity (CC50) against Vero cells of 25 mu g/mL. 20q also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. 20q was also negative in a L5178Y MOLY assay, indicating low potential for genetic toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs.

  DOI：

  10.1021/jm300123s

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。
• [EN] SUBSTITUTED BENZOTRIAZINES AND QUINOXALINES AS INHIBITORS OF P7OS6 KINASE<br/>[FR] BENZOTRIAZINES ET QUINOXINALINES SUBSTITUÉES COMME INHIBITEURS DE LA P7OS6 KINASE
  申请人：SENTINEL ONCOLOGY LTD

  公开号：WO2010136755A1

  公开（公告）日：2010-12-02

  The invention provides compounds of the formula (1): or salts or tautomers thereof; wherein X1 is N or N+(O ); X2 is N or CH; Q is a C1-3 alkylene group; R1 is selected from hydrogen, C1-4 hydrocarbyl and hydroxy-C2-4 hydrocarbyl; R2, R3 and R4 are the same or different and each is selected from hydrogen, fluorine, chlorine and methyl; Ar1 is an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring containing 0, 1 or 2 heteroatom ring members selected from O, N and S, or a naphthyl ring and Ar2 is an optionally substituted monocyclic 5 or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S. The compounds of formula (1) are inhibitors of p70S6 kinase and are useful in the treatment of proliferative diseases.

  该发明提供了式（1）的化合物或其盐或互变异构体；其中X1为N或N+（O-）；X2为N或CH；Q为C1-3烷基基团；R1从氢、C1-4烃基和羟基-C2-4烃基中选择；R2、R3和R4相同或不同，每个从氢、氟、氯和甲基中选择；Ar1为含有0、1或2个来自O、N和S的杂原子环成员的可选择取代的单环5或6成员芳基或杂芳基环，或者是一个萘环；Ar2为含有1、2或3个来自O、N和S的杂原子环成员的可选择取代的单环5或6成员杂芳基环。式（1）的化合物是p70S6激酶的抑制剂，可用于治疗增殖性疾病。
• [EN] MODULATORS OF THE P70S6 KINASE FOR USE IN THE TREATMENT OF BRAIN DISORDERS AND TRIPLE-NEGATIVE BREAST CANCER<br/>[FR] MODULATEURS DE LA P70S6 KINASE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE TROUBLES CÉRÉBRAUX ET DU CANCER DU SEIN TRIPLE NÉGATIF
  申请人：SENTINEL ONCOLOGY LTD

  公开号：WO2016131776A1

  公开（公告）日：2016-08-25

  The invention provides compounds for use in the treatment of a disease or condition selected from brain disorders and triple-negative breast cancer, the compounds being of the formula (1) or a salt or tautomer thereof; wherein: X1 is N or N+(O'); X2 is N or CH; Q is selected from a C1-3 alkylene group, cyclopropane-1,1-diyl and cyclobutane- 1,1-diyl; R1 is selected from hydrogen and C1-4 alkyl;R2, R3 and R4 are the same or different and each is selected from hydrogen and fluorine; Ar1 is a benzene, thiophene, naphthyl or pyridine ring optionally substituted with 1, 2 or 3 substituents selected from fluorine; chlorine; bromine; CM hydrocarbyl; C1-4 hydrocarbyloxy; trifluoromethyl; difluoromethyl; cyano; trifluoromethoxy; difluoromethoxy; Ar2 is a monocyclic 5- or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S and being optionally substituted with 1, 2 or 3 substituents selected from fluorine; C1-4 hydrocarbyl; amino; mono-C1-4 hydrocarbylamino and di-C1-4 hydrocarbylamino; and wherein, in each substituent consisting of or containing C1-4 hydrocarbyl, the C1-4 hydrocarbyl is selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, cyclopropyl, cyclobutyl and cyclopropylmethyl.

  该发明提供了用于治疗脑部疾病和三阴性乳腺癌等疾病或症状的化合物，该化合物为以下公式（1）或其盐或互变异构体；其中：X1为N或N+(O')；X2为N或CH；Q从C1-3烷基、环丙烷-1,1-二基和环丁烷-1,1-二基中选择；R1从氢和C1-4烷基中选择；R2、R3和R4相同或不同，每个从氢和氟中选择；Ar1为苯、噻吩、萘或吡啶环，可选择地取代1、2或3个从氟、氯、溴、CM烃基、C1-4烃基氧、三氟甲基、二氟甲基、氰、三氟甲氧基、二氟甲氧基中选择的取代基；Ar2为含有1、2或3个来自O、N和S的杂原子环成员的单环5-或6-成员杂环环，可选择地取代1、2或3个从氟、C1-4烃基、氨基、单C1-4烃基氨基和双C1-4烃基氨基中选择的取代基；在每个由或含有C1-4烃基的取代基中，C1-4烃基从C1-4烷基、C2-4烯基、C2-4炔基、环丙基、环丁基和环丙基甲基中选择。
• 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
• Application of Suzuki-Miyaura and Buchwald<i>-</i>Hartwig Cross-coupling Reactions to the Preparation of Substituted 1,2,4-Benzotriazine 1-Oxides Related to the Antitumor Agent Tirapazamine
  作者：Ujjal Sarkar、Roman Hillebrand、Kevin M. Johnson、Andrea H. Cummings、Ngoc Linh Phung、Anuruddha Rajapakse、Haiying Zhou、Jordan R. Willis、Charles L. Barnes、Kent S. Gates

  DOI：10.1002/jhet.2559

  日期：2017.1

  there is a desire for synthetic routes that afford access to substituted 1,2,4-benzotriazine 1-oxides that can be used as direct precursors in the synthesis of 1,2,4-benzotriazine 1,4-dioxides. Here we describe the use of Suzuki-Miyaura and Buchwald-Hartwig cross-coupling reactions for the construction of various 1,2,4-benzotriazine 1-oxide analogs bearing substituents at the 3-, 6-, and 7-positions

  许多1,2,4-苯并三嗪1,4-二氧化物具有选择性杀死实体瘤中缺氧细胞的能力。结果，期望提供能够获得取代的1,2,4-苯并三嗪1-氧化物的合成路线，所述取代的1,2,4-苯并三嗪1-氧化物可用作1,2,4-苯并三嗪1,4-二氧化物的直接前体。在这里，我们描述了使用Suzuki-Miyaura和Buchwald-Hartwig交叉偶联反应来构建各种在3、6和7位带有取代基的1,2,4-苯并三嗪1-氧化物类似物。