3-chloro-7-fluoro-1,2,4-benzotriazine 1-oxide | 78689-29-9

• 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: 3-chloro-7-fluoro-1,2,4-benzotriazine 1-oxide
• 英文别名: 3-chloro-7-fluorobenzo[e][1,2,4]triazine 1-oxide；3-chloro-7-fluoro-1-oxido-1,2,4-benzotriazin-1-ium
• CAS: 78689-29-9
• 化学式: C₇H₃ClFN₃O
• 分子量: 199.572
• InChiKey: HPIPWXDSZNNJNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 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：
  51.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-chloro-7-fluoro-1,2,4-benzotriazine 1-oxide 在 四(三苯基膦)钯 sodium 作用下， 以 乙腈 为溶剂， 反应 2.33h， 生成 3-ethyl-7-methoxy-1,2,4-benzotriazine 1-oxide
  参考文献：
  名称：

  Stille Coupling Reactions in the Synthesis of Hypoxia-Selective 3-Alkyl-1,2,4-Benzotriazine 1,4-Dioxide Anticancer Agents

  摘要：

  The introduction of a 3-alkyl substituent is a key step in the synthesis of 1,2,4-benzotriazine 1,4-dioxide hypoxia-selective anticancer agents, such as SN29751. The Stille reaction of 3-chloro-1,2,4-benzotriazine 1-oxides ( BTOs) 5 was inhibited by the presence of electron donating substituents on the benzo ring, thus limiting the range of compounds available for SAR studies. The use of 3-iodo-BTOs 8 did not provide a significant improvement in the yields of 3-ethyl-BTOs 6. Microwave-assisted Stille coupling of chlorides 5 gave dramatically improved yields, which were consistently superior to those from the corresponding iodides 8. The application of microwave-assisted synthesis extended the range of substituted BTOs available for SAR studies and provided an efficient, scalable synthesis of the investigational anticancer agent, SN29751 ( 1).

  DOI：

  10.1021/jo060986g
• 作为产物：
  描述：

  4-氟-2-硝基苯胺 在 三氟乙酸 、 sodium hydroxide 、 sodium nitrite 作用下， 生成 3-chloro-7-fluoro-1,2,4-benzotriazine 1-oxide
  参考文献：
  名称：

  [EN] BENZOTRIAZINE DIOXIDE AND PHARMACEUTICAL COMPOSITION THEREOF
  [FR] DIOXYDE DE BENZOTRIAZINE ET COMPOSITION PHARMACEUTIQUE ASSOCIÉE
  [ZH] 苯并三嗪双氧化物及其药物组合物

  摘要：

  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。

  公开号：

  WO2023019912A1

文献信息

• Spin Trapping Hydroxyl and Aryl Radicals of One-Electron Reduced Anticancer Benzotriazine 1,4-Dioxides
  作者：Wen Qi、Pooja Yadav、Cho R. Hong、Ralph J. Stevenson、Michael P. Hay、Robert F. Anderson

  DOI：10.3390/molecules27030812

  日期：——

  electron spin resonance, give evidence for the formation of aryl radicals from compounds 1, 2 and 3-phenyl analogues, compounds 3 and 4, which form carbon C-centered radicals. In addition, high concentrations of DEPMPO (5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide) spin-trap the •OH radical. The combination of spin-traps with high concentrations of DMSO and methanol also give evidence for the involvement

  肿瘤中的缺氧导致对化学疗法和放射疗法治疗的抵抗，但提供了一种环境，其中缺氧激活的前药（HAP）在生物还原后被激活以释放靶向细胞毒素。苯并三嗪 1,4-二-N-氧化物 (BTO) HAP、替拉扎明 (TPZ, 1) 已与放射疗法联合进行了广泛的临床评估，以帮助杀死缺氧的肿瘤细胞。尽管化合物 1 没有获得临床使用批准，但它促进了其他 BTO 的开发，例如 3-烷基类似物 SN30000, 2。普遍认为 BTO 中的细胞毒素来自化合物的电子还原形式。识别细胞毒性自由基，以及它们是否在选择性杀死缺氧肿瘤细胞中起作用，对于 BTO 类抗癌前药的持续开发很重要。在这项研究中，硝酮自旋陷阱与电子自旋共振相结合，为化合物 1、2 和 3-苯基类似物、化合物 3 和 4 形成芳基自由基提供了证据，这些化合物形成以碳 C 为中心的自由基。此外，高浓度的 DEPMPO (5-(二乙氧基磷酰基)-5-甲基-1-吡咯啉
• 1,2,4-Benzotriazinyloxyphenoxyalkane carboxylic-acid derivatives, processes for their preparation, their use as herbicides, and their preparation
  申请人：ICI AUSTRALIA LIMITED

  公开号：EP0024932A2

  公开（公告）日：1981-03-11

  The invention concerns novel compounds of the formula I The compounds are herbicides and in further embodiments the invention provides processesforthe preparation of compounds of formula I, intermediates useful in the preparation of compounds of formula I, herbicidal compositions containing as active ingredient a compound of formula 1, and processes for severely damaging or killing unwanted plants by applying to the plants or to the growth medium of the plants an effective amount of a compound of formula I.

  本发明涉及式 I 的新型化合物 这些化合物是除草剂，在进一步的实施方案中，本发明提供了制备式 I 化合物的工艺、用于制备式 I 化合物的中间体、含有作为活性成分的式 1 化合物的除草组合物，以及通过向植物或植物的生长介质施用有效量的式 I 化合物来严重损害或杀死不需要的植物的工艺。
• Herbicidal aryloxybenzeneacetic acid derivatives
  申请人：E.I. DU PONT DE NEMOURS AND COMPANY

  公开号：EP0206772A2

  公开（公告）日：1986-12-30

  Compounds of the formula wherein A is specified nitrogen-containing heterocycle; R is H2 halogen, CH3, OCH3 or OC2H5; Ri is C1-C3 alkyl, allyl or propargyl; R2 is X1R8 or OH; X1 is 0 or S; and R8 is an organic group; and their agriculturally suitable salts, exhibit herbicidal activity, especially for the selective control of weeds in rice. The compound may be made by a variety of synthetic routes, e.g. by reacting a haloheterocycle of formula A - Hal with an alkali metal salt of the appropriate 4-hydroxy-benzene- acetate ester.

  式中的化合物 其中 A 为指定的含氮杂环； R 是 H2 卤素、CH3、O 或 OC2H5； Ri 是 C1-C3 烷基、烯丙基或丙炔基； R2 是 X1R8 或 OH； X1 是 0 或 S；以及 R8 是有机基团；以及它们在农业上适用的盐，具有除草活性，特别是在选择性控制水稻杂草方面。 该化合物可通过多种合成途径制得，例如通过式 A - Hal 的卤代杂环与碱金属反应 A - Hal 与适当的 4-羟基苯乙酸酯的碱金属盐反应。
• Discovery and Optimization of Benzotriazine Di-<i>N</i>-Oxides Targeting Replicating and Nonreplicating Mycobacterium tuberculosis
  作者：Sidharth Chopra、Gary A. Koolpe、Arlyn A. Tambo-ong、Karen N. Matsuyama、Kenneth J. Ryan、Tran B. Tran、Rupa S. Doppalapudi、Edward S. Riccio、Lalitha V. Iyer、Carol E. Green、Baojie Wan、Scott G. Franzblau、Peter B. Madrid

  DOI：10.1021/jm300123s

  日期：2012.7.12

  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.
• US4309211A
  申请人：——

  公开号：US4309211A

  公开（公告）日：1982-01-05