3-氯-7-甲氧基-1,2,4-苯并三嗪1-氧化物 | 62843-73-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 3-氯-7-甲氧基-1,2,4-苯并三嗪1-氧化物
• 英文名称: 3-chloro-7-methoxy-1,2,4-benzotriazine 1-oxide
• 英文别名: 3-chloro-7-methoxy-benzo[e][1,2,4]triazine 1-oxide；3-Chlor-7-methoxy-benzo[e][1,2,4]triazin-1-oxid；3-chloro-7-methoxy-1 ,2,4-benzotriazine 1-oxide；3-Chlor-7-methoxy-benzo-1,2,4-triazin-1-oxid；3-chloro-7-methoxy-1-oxido-1,2,4-benzotriazin-1-ium
• CAS: 62843-73-6
• 化学式: C₈H₆ClN₃O₂
• 分子量: 211.608
• InChiKey: HPAGZENHZFGZRB-UHFFFAOYSA-N

物化性质

• 熔点：
  177-179 °C(Solv: ethyl acetate (141-78-6); dichloromethane (75-09-2))
• 沸点：
  423.0±37.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氯-7-甲氧基-1,2,4-苯并三嗪1-氧化物 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 甲醇 、 丁酮 为溶剂， 反应 7.0h， 生成 methyl 2-{4-[(7-methoxy-1,2,4-benzotriazin-3-yl)oxy]phenoxy}propionate
  参考文献：
  名称：

  二。抗肿瘤药2-（4-[（7-氯-2-喹喔啉基）氧基]苯氧基）丙酸（XK469）的一些生物等排体和同类物的合成和生物学评估。

  摘要：

  XK469（1）是我们实验室中评估的最高度和最广泛活性的抗肿瘤药物之一。随后的开发研究导致（R）-（+）1（NSC 698215）进入1期临床试验（NIH UO1-CA62487）。1的抗肿瘤作用机理尚待阐明，这促使人们不断努力拟订1的药效学模式。本研究的重点是对喹喔啉部分中基于拓扑的生物等位替代物进行合成和生物学评估的策略。铅化合物（1）由喹唑啉（4a-d），1,2,4-苯并三嗪（12a-18b）和喹啉（21a-g）环系统合成。对每个1的生物等排体的合成方法都采用了先前工作中开发的方法（请参见ST的Hazeldine； L。的Polin； J。的Kushner； J。的Paluch； J。的White； K.Edelstein； M。的Palomino，E .; TH，Corbett；Horwitz，JP设计，合成和抗肿瘤药2-（4-[（7-氯-2-喹喔啉基）氧基]苯氧基）丙酸（XK469）类似物的生物学评估。J

  DOI：

  10.1021/jm0200097
• 作为产物：
  描述：

  4-甲氧基-2-硝基乙酰苯胺 在 盐酸 、 三氟乙酸 、 sodium nitrite 、 三氯氧磷 作用下， 以 乙醚 、 水 为溶剂， 反应 11.0h， 生成 3-氯-7-甲氧基-1,2,4-苯并三嗪1-氧化物
  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。
• 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。
• Fungicidal cyclic amides
  申请人：E. I. du Pont de Nemours and Company

  公开号：US05962436A1

  公开（公告）日：1999-10-05

  Cyclic amides, including triazole containing cyclic amides, their N-oxides, agriculturally-suitable salts and compositions, and their methods of use as fungicides.

  环状酰胺，包括三唑环状酰胺，它们的N-氧化物，适用于农业的盐和组合物，以及它们作为杀真菌剂的使用方法。
• Stille Coupling Reactions in the Synthesis of Hypoxia-Selective 3-Alkyl-1,2,4-Benzotriazine 1,4-Dioxide Anticancer Agents
  作者：Karin Pchalek、Michael P. Hay

  DOI：10.1021/jo060986g

  日期：2006.8.1

  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).
• Syntheses in the 1,2,4-Benzotriazine Series
  作者：JAMES JIU、GEORGE P. MUELLER

  DOI：10.1021/jo01088a021

  日期：1959.6