7-chloro-1-oxido-1,2,4-benzotriazin-1-ium-3-ol | 20028-78-8

• 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-oxido-1,2,4-benzotriazin-1-ium-3-ol
• 英文别名: 7-chloro-1-oxy-4H-benzo[1,2,4]triazin-3-one；7-chloro-1-oxy-benzo[1,2,4]triazin-3-ol；7-chloro-1-oxido-2H-1,2,4-benzotriazin-1-ium-3-one
• CAS: 20028-78-8
• 化学式: C₇H₄ClN₃O₂
• 分子量: 197.581
• InChiKey: DPUQPGUHZJMJFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 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-chloro-1-oxido-1,2,4-benzotriazin-1-ium-3-ol 在 三氯氧磷 作用下， 以89%的产率得到3,7-dichloro-1-oxido-1,2,4-benzotriazin-1-ium
  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：

  N-(4-氯-2-硝基苯基)乙酰胺 在 盐酸 、 三氟乙酸 、 sodium nitrite 作用下， 以 乙醚 、 水 为溶剂， 反应 8.0h， 生成 7-chloro-1-oxido-1,2,4-benzotriazin-1-ium-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。
• [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。
• 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。
• 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。
• Syntheses in the 1,2,4-Benzotriazine Series
  作者：JAMES JIU、GEORGE P. MUELLER

  DOI：10.1021/jo01088a021

  日期：1959.6