3-iodo-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1-oxide | 910105-75-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 3-iodo-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1-oxide
• 英文别名: 3-iodo-1-oxido-7,8-dihydro-6H-cyclopenta[g][1,2,4]benzotriazin-1-ium
• CAS: 910105-75-8
• 化学式: C₁₀H₈IN₃O
• 分子量: 313.098
• InChiKey: BNVFMQQRYOSQHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  51.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-iodo-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1-oxide 在 四(三苯基膦)钯 ZnCl2.Et2O 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 1.17h， 以56%的产率得到3-ethyl-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1-oxide
  参考文献：
  名称：

  WO2006/104406

  摘要：

  公开号：
• 作为产物：
  描述：

  7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-oxide 在 copper(l) iodide 亚硝酸特丁酯 、 碘 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以81%的产率得到3-iodo-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 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

文献信息

• Benzotriazine Di-Oxide Prodrugs for Exploiting Hypoxia and Low Extracellular pH in Tumors
  作者：Michael P. Hay、Hong Nam Shin、Way Wua Wong、Wan Wan Sahimi、Aaron T.D. Vaz、Pooja Yadav、Robert F. Anderson、Kevin O. Hicks、William R. Wilson

  DOI：10.3390/molecules24142524

  日期：——

  feature of tumor microenvironments but has yet to be successfully exploited in cancer therapy. The reversal of the pH gradient across the plasma membrane in cells that regulate intracellular pH (pHi) has potential to drive the selective uptake of weak acids at low extracellular pH (pHe). Here, we investigate the dual targeting of low pHe and hypoxia, another key feature of tumor microenvironments. We prepared

  细胞外酸化是肿瘤微环境的一个重要特征，但尚未在癌症治疗中成功利用。调节细胞内 pH (pHi) 的细胞质膜 pH 梯度的逆转有可能驱动低细胞外 pH (pHe) 下弱酸的选择性摄取。在这里，我们研究了低 pHe 和缺氧的双重靶向，这是肿瘤微环境的另一个关键特征。我们通过附加链烷酸或氨基链烷酸侧链，制备了基于二氧化苯并三嗪（BTO）核的八种生物还原前药。BTO 酸在 SiHa 和 FaDu 细胞培养物中对低 pHe（pH 6.5 与 7.4，比率 2 至 5 倍）和缺氧（比率 2 至 8 倍）表现出适度的选择性。相关的中性 BTO 对酸中毒没有选择性，但比 BTO 酸具有更大的细胞毒性效力和缺氧选择性。对代表性 BTO 酸的摄取和代谢的研究证实，在低 pHe 下摄取增强，但细胞内浓度低于被动扩散的预期。此外，细胞内还原酶活性的调节和细胞排斥电子受体 WST-1 的竞争表明，BTO 酸的大部分
• 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。
• [EN] SULFONAMIDE, SULFAMATE AND SULFAMIDE DERIVATIVES OF ANTI-CANCER AGENTS<br/>[FR] DÉRIVÉS SULFONAMIDE, SULFAMATE ET SULFAMIDE D'AGENTS ANTICANCÉREUX
  申请人：STICHTING MAASTRICHT RADIATION ONCOLOGY MAASTRO-CLINIC

  公开号：WO2016089208A3

  公开（公告）日：2016-09-01
• 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