6-methoxy-1-oxy-4H-benzo[e][1,2,4]triazin-3-one | 27446-09-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-methoxy-1-oxy-4H-benzo[e][1,2,4]triazin-3-one
• 英文别名: 6-methoxy-1-oxido-2H-1,2,4-benzotriazin-1-ium-3-one
• CAS: 27446-09-9
• 化学式: C₈H₇N₃O₃
• 分子量: 193.162
• InChiKey: WQWFWTRXJCNUHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 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：
  79.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-methoxy-1-oxy-4H-benzo[e][1,2,4]triazin-3-one 在 四(三苯基膦)钯 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.33h， 生成 3-乙基-6-甲氧基-1,2,4-苯并三嗪1-氧化物
  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：

  3-amino-6-methoxybenzo[e][1,2,4]triazine 1-oxide 在 硫酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 0.25h， 以90%的产率得到6-methoxy-1-oxy-4H-benzo[e][1,2,4]triazin-3-one
  参考文献：
  名称：

  II型细菌拓扑异构酶的新型N-联氨基哌啶抑制剂：hERG活性降低的广谱抗菌剂

  摘要：

  新型的细菌II型拓扑异构酶的非氟喹诺酮抑制剂（DNA促旋酶和拓扑异构酶IV）对于开发不受靶标介导的氟喹诺酮类交叉耐药性影响的新型抗菌剂具有重要意义。具有通过碳与乙基桥连接的双环芳族部分的氨基哌啶，例如1，通常显示出强效的广谱抗菌活性，包括对喹诺酮类耐药的菌株，但受到强的hERG抑制作用（IC 50 = 3μM/ 1） 。我们现在公开的发现是，新的1的类似物具有连接到乙基桥的N-连接的环状酰胺部分，例如24m，保留了其的广谱抗菌活性。1，但显示出显着更少的hERG抑制作用（24 m时IC 50 = 31μM）和高于1的游离分数。一种优化的类似物化合物24l在狗的大腿感染模型中在狗中表现出中等清除率，并且有望抵抗金黄色葡萄球菌。

  DOI：

  10.1021/jm2008826

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。
• 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).
• Novel N-Linked Aminopiperidine Inhibitors of Bacterial Topoisomerase Type II: Broad-Spectrum Antibacterial Agents with Reduced hERG Activity
  作者：Folkert Reck、Richard Alm、Patrick Brassil、Joseph Newman、Boudewijn DeJonge、Charles J. Eyermann、Gloria Breault、John Breen、Janelle Comita-Prevoir、Mark Cronin、Hajnalka Davis、David Ehmann、Vincent Galullo、Bolin Geng、Tyler Grebe、Marshall Morningstar、Phil Walker、Barry Hayter、Stewart Fisher

  DOI：10.1021/jm2008826

  日期：2011.11.24

  isolates, but suffer from potent hERG inhibition (IC50= 3 μM for 1). We now disclose the finding that new analogues of 1 with an N-linked cyclic amide moiety attached to the ethyl bridge, such as 24m, retain the broad-spectrum antibacterial activity of 1 but show significantly less hERG inhibition (IC50= 31 μM for 24m) and higher free fraction than 1. One optimized analogue, compound 24l, showed moderate

  新型的细菌II型拓扑异构酶的非氟喹诺酮抑制剂（DNA促旋酶和拓扑异构酶IV）对于开发不受靶标介导的氟喹诺酮类交叉耐药性影响的新型抗菌剂具有重要意义。具有通过碳与乙基桥连接的双环芳族部分的氨基哌啶，例如1，通常显示出强效的广谱抗菌活性，包括对喹诺酮类耐药的菌株，但受到强的hERG抑制作用（IC 50 = 3μM/ 1） 。我们现在公开的发现是，新的1的类似物具有连接到乙基桥的N-连接的环状酰胺部分，例如24m，保留了其的广谱抗菌活性。1，但显示出显着更少的hERG抑制作用（24 m时IC 50 = 31μM）和高于1的游离分数。一种优化的类似物化合物24l在狗的大腿感染模型中在狗中表现出中等清除率，并且有望抵抗金黄色葡萄球菌。