7-bromo-1-oxybenzo[1,2,4]triazin-3-ol | 70373-30-7

• 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: 7-bromo-1-oxybenzo[1,2,4]triazin-3-ol
• 英文别名: 7-bromo-1-oxy-benzo[1,2,4]triazin-3-ol；7-bromo-1-oxido-2H-1,2,4-benzotriazin-1-ium-3-one
• CAS: 70373-30-7
• 化学式: C₇H₄BrN₃O₂
• mdl: MFCD21145577
• 分子量: 242.032
• InChiKey: ZMKANKBILYKILO-UHFFFAOYSA-N

物化性质

• 熔点：
  249-253 °C
• 密度：
  2.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 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：
  70.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-bromo-1-oxybenzo[1,2,4]triazin-3-ol 在 氯化铵 、 锌 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 32.0h， 生成 7-bromo-3-chlorobenzo[1,2,4]triazine
  参考文献：
  名称：

  [EN] SUBSTITUTED QUINOXALINES AND BENZOTRIAZINE P70S6 KINASE INHIBITORS
  [FR] INHIBITEURS DE TYPE QUINOXALINES ET BENZOTRIAZINE SUBSTITUÉES DE LA P70S6 KINASE

  摘要：

  该发明提供了抑制或调节p70S6激酶活性的化合物，该化合物的结构如下式（0），或其盐、互变异构体或N-氧化物；其中：X1为N或N+(0-)；X2为N或CH；Q1为可选择取代的C1-8烷基；Q2为键或可选择取代的C1-8烷基基团；R1选自氢和Cy1基团；Cy1为可选择取代的含有0、1或2个来自O和S的杂原子环成员的4到7成员单环非芳香碳环或杂环基团及S的氧化形式；R2、R3和R4相同或不同，每个选自氢、氟、氯、C1-2烷基和C1-2烷氧基，其中每个C1-2烷基和C1-2烷氧基可选择地取代为两个或更多氟原子；Ar1为可选择取代的含有0、1或2个来自O、N和S的杂原子环成员的单环5或6成员芳基或杂芳基环，或一个萘环；Ar2为可选择取代的含有1、2、3或4个来自O、N和S的杂原子环成员的双环8到11成员杂芳基基团。这些化合物在医学上有用，例如在治疗癌症（如三阴性乳腺癌、脑肿瘤和来自非脑部癌症的脑转移瘤）、神经发育疾病（如脆性X综合征）和神经退行性疾病等疾病或病况的治疗中。

  公开号：

  WO2016170163A1
• 作为产物：
  描述：

  4'-溴乙酰苯胺 在 盐酸 、 硝酸 、 乙酸酐 、 三氟乙酸 、 sodium nitrite 作用下， 以 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 8.0h， 生成 7-bromo-1-oxybenzo[1,2,4]triazin-3-ol
  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

• [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。
• The tert-butyl-NNO-azoxy group in the synthesis of 1,2,4-benzotriazin-3(4H)-one 1-oxides
  作者：D. L. Lipilin、A. M. Churakov、Yu. A. Strelenko、V. A. Tartakovsky

  DOI：10.1007/s11172-007-0244-4

  日期：2007.8

  novel route to 1,2,4-benzotriazin-3(4H )-one 1-oxides. This method involves a new reaction, viz., an intramolecular interaction of the tert-butyl-NNO-azoxy group with a C-electrophile (leading to the formation of the N(2)—C(3) bond of the triazine ring) followed by elimination of the tert-butyl group. Complete assignment of the signals in the 1H and 13C NMR spectra of the compounds obtained was performed

  提出了在 20 °C 下用光气处理 2-(叔丁基-NNO-偶氮氧基)苯胺作为制备 1,2,4-苯并三嗪-3(4H )-one 1-氧化物的新途径。该方法涉及一个新反应，即叔丁基-NNO-偶氮氧基与 C-亲电试剂的分子内相互作用（导致三嗪环的 N(2)-C(3) 键的形成）然后消除叔丁基。对所得化合物的 1H 和 13C NMR 光谱中的信号进行了完全分配。
• SUBSTITUTED BENZOTRIAZINES AND QUINOXALINES AS INHIBITORS OF P7OS6 KINASE
  申请人：Boyle Robert George

  公开号：US20120071478A1

  公开（公告）日：2012-03-22

  The invention provides compounds of the formula (1): or salts or tautomers thereof; wherein X 1 is N or N + (O − ); X 2 is N or CH; Q is a C 1-3 alkylene group; R 1 is selected from hydrogen, C 1-4 hydrocarbyl and hydroxy-C 2-4 hydrocarbyl; R 2 , R 3 and R 4 are the same or different and each is selected from hydrogen, fluorine, chlorine and methyl; Ar 1 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 Ar 2 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.

  本发明提供公式（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选择自氢，C1-4烃基和羟基-C2-4烃基; R2，R3和R4相同或不同，且每个选择自氢，氟，氯和甲基; Ar1为含有0、1或2个杂环环成员（选自O，N和S）的可选择取代的单环5或6成员芳基或杂芳基环，或萘环；Ar2为含有1、2或3个杂环环成员（选自O，N和S）的可选择取代的单环5或6成员杂芳基环。公式（1）的化合物是p70S6激酶的抑制剂，可用于治疗增生性疾病。
• Substituted benzotriazines and quinoxalines as inhibitors of P7OS6 kinase
  申请人：Boyle Robert George

  公开号：US08716473B2

  公开（公告）日：2014-05-06

  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.

  本发明提供式（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; R1选自氢，C1-4烃基和羟基-C2-4烃基; R2，R3和R4相同或不同，且每个选自氢，氟，氯和甲基; Ar1为可选取代的单环5或6成员芳基或杂芳基环，其中包含0，1或2个杂原子环成员，选自O，N和S，或萘环；Ar2为可选取代的单环5或6成员杂芳基环，其中包含1，2或3个杂原子环成员，选自O，N和S。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] BENZOTRIAZINE DIOXIDE AND PHARMACEUTICAL COMPOSITION THEREOF<br/>[FR] DIOXYDE DE BENZOTRIAZINE ET COMPOSITION PHARMACEUTIQUE ASSOCIÉE<br/>[ZH] 苯并三嗪双氧化物及其药物组合物
  申请人：[en]HANGZHOU RAYGENE PHARMACEUTICAL CO., LTD.;[zh]杭州瑞臻医药有限公司

  公开号：WO2023019912A1

  公开（公告）日：2023-02-23

  具有以下通式(I)的苯并三嗪双氧化物或其药学上可接受的盐或酯、水合物、溶剂化物或前药，还提供组合物以及治疗癌症的方法。