[1,3]dioxolo[4,5-g][1,2,4]benzotriazin-3-amine 1-oxide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: [1,3]dioxolo[4,5-g][1,2,4]benzotriazin-3-amine 1-oxide
• 英文别名: 1-oxido-[1,3]dioxolo[4,5-g][1,2,4]benzotriazin-1-ium-3-amine
• 化学式: C₈H₆N₄O₃
• 分子量: 206.161
• InChiKey: WNFOHBLMGZFNLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  95.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [1,3]dioxolo[4,5-g][1,2,4]benzotriazin-3-amine 1-oxide 在 双氧水 、 三氟乙酸 、 三氟乙酸酐 、 sodium nitrite 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 12.75h， 生成 N1-(1,4-dioxido-[1,3]dioxolo[4,5-g][1,2,4]benzotriazin-3-yl)-N2,N2-dimethyl-1,2-ethanediamine
  参考文献：
  名称：

  WO2006/104406

  摘要：

  公开号：
• 作为产物：
  描述：

  3,4-亚甲基二氧基乙酰苯胺 在 硝酸 、 sodium methylate 作用下， 以 甲醇 、 水 、 溶剂黄146 为溶剂， 反应 23.25h， 生成 [1,3]dioxolo[4,5-g][1,2,4]benzotriazin-3-amine 1-oxide
  参考文献：
  名称：

  WO2006/104406

  摘要：

  公开号：

文献信息

• [EN] DEVELOPMENT OF INJECTABLE FIDUCIAL MARKERS FOR IMAGE GUIDED RADIOTHERAPY WITH DUAL MRI AND CT VISIBILITY<br/>[FR] DÉVELOPPEMENT DE MARQUEURS DE RÉFÉRENCE INJECTABLES POUR RADIOTHÉRAPIE GUIDÉE PAR L'IMAGE AVEC DOUBLE VISIBILITÉ IRM ET CT
  申请人：UNIV DENMARK TECH DTU

  公开号：WO2018215595A1

  公开（公告）日：2018-11-29

  Radiation therapy or radiotherapy (RT) is a powerful treatment where precision and accuracy is crucial. Image Guided Radiotherapy (IGRT) facilitates more accurate position verification, correcting for anatomic changes related to internal organ movement. IGRT thereby helps reduce toxicity of radiotherapy and increases relapse-free survival. Currently, the most frequently used imaging-technique for IGRT is Computed Tomography (CT). However, CT- based target delineation of soft tissue tumors tends to only improve the precision and not the accuracy of treatment due to its relatively low soft tissue resolution. In some tumors ∼40% larger volumes are defined on CT compared to MRI, a technique with submillimeter soft tissue resolution. Therefore, it is advantageous to apply both CT and MRI in planning of soft tissue tumor radiotherapy. An inter-correlation point with a fixed position and volume (a marker) can be applied to indicate the point of treatment clearly in both imaging modalities and to localize and track tumors in real time. In this study, we present the development of a marker based on lactose octaacetate:octapropionate 1 :1 containing 3 mM PLA-DTPA(Gd), 40% triglyceride, 5% propylene carbonate and 10% XSAIB (sucrose based CT-contrast agent). The injectable marker had high CT contrast (>1000 HU) and displayed clearly visible, stable Ti contrast enhancement (T1 ∼900 ms) in the rim over at least 3 weeks with clinically observable resolution. Key words: Fiducial marker, MRI, CT, Image Guided Radiotherapy

  放射治疗或放射疗法（RT）是一种精度和准确性至关重要的强大治疗方法。图像引导放射治疗（IGRT）有助于更准确地验证位置，纠正与内部器官运动相关的解剖学变化。IGRT因此有助于减少放射治疗的毒性并增加无复发生存率。目前，IGRT最常用的成像技术是计算机断层扫描（CT）。然而，基于CT的软组织肿瘤靶区划分往往只能提高精度而不能提高治疗的准确性，因为其软组织分辨率相对较低。在某些肿瘤中，与MRI相比，CT定义的体积大约增加了40％，MRI是一种具有亚毫米软组织分辨率的技术。因此，在软组织肿瘤放射治疗的规划中同时应用CT和MRI是有利的。可以应用具有固定位置和体积（标记）的相互关联点来清楚地指示治疗点在两种成像模式中的位置，并实时定位和跟踪肿瘤。在本研究中，我们介绍了一种基于乳糖八酸酯：八丙酸酯1：1的标记的开发，其中含有3 mM PLA-DTPA（Gd），40％甘油三酯，5％丙烯酸碳酸酯和10％XSAIB（基于蔗糖的CT对比剂）。可注射标记具有高CT对比度（> 1000 HU），并在至少3周的时间内显示出明显可见的、稳定的Ti对比增强（T1约为900毫秒）的边缘，具有临床可观察的分辨率。关键词：基准标记，MRI，CT，图像引导放射治疗
• Tricyclic 1,2,4-triazine oxides and compositions for therapeutic use in cancer treatments
  申请人：Auckland Uniservices Limited

  公开号：US07989451B2

  公开（公告）日：2011-08-02

  The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula I and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

  本发明涉及新型三环1,2,4-三嗪-1-氧化物和新型三环1,2,4-三嗪-1,4-二氧化物的公式I以及相关类似物，涉及它们的制备，以及它们作为缺氧选择性药物和放射增敏剂用于癌症治疗，无论是单独使用还是与放射治疗和/或其他抗癌药物联合使用。
• Tricyclic 1,2,4-Triazine Oxides and Compositions for Therapeutic Use in Cancer Treatments
  申请人：Hay Michael Patrick

  公开号：US20090186886A1

  公开（公告）日：2009-07-23

  The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula I and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

  本发明涉及新型三环1,2,4-三嗪-1-氧化物和新型三环1,2,4-三嗪-1,4-二氧化物的公式I以及相关类似物，它们的制备以及它们作为低氧选择性药物和放射增敏剂用于癌症治疗，可以单独使用或与放射线和/或其他抗癌药物联合使用。
• Tricyclic [1,2,4]Triazine 1,4-Dioxides As Hypoxia Selective Cytotoxins
  作者：Michael P. Hay、Kevin O. Hicks、Karin Pchalek、Ho H. Lee、Adrian Blaser、Frederik B. Pruijn、Robert F. Anderson、Sujata S. Shinde、William R. Wilson、William A. Denny

  DOI：10.1021/jm800967h

  日期：2008.11.13

  A series of novel tricyclic triazine-di-N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen-, and nitrogen-containing Saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia-selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion coefficients were achieved with fused cycloalkyl rings in combination with both the 3-aminoalkyl or 3-alkyl substituents linked to weakly basic soluble amines. The selection was further refined 7 using pharmacokinetic/phamacodynamic model predictions of the in vivo hypoxic potency (AUC(req)) and selectivity (HCD) with 12 TTO analogues predicted to be active in Vivo, Subject to the achievement of adequate plasma pharmacokinetics.
• TRICYCLIC 1,2,4-TRIAZINE OXIDES AND COMPOSITIONS THEREFROM FOR THERAPEUTIC USE IN CANCER TREATMENTS
  申请人：AUCKLAND UNISERVICES LIMITED

  公开号：EP1866292B1

  公开（公告）日：2010-12-15