N¹-(1,4-dioxido-1,2,4-benzotriazin-3-yl)-1,6-hexanediamine | 676350-16-6

• 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: N¹-(1,4-dioxido-1,2,4-benzotriazin-3-yl)-1,6-hexanediamine
• 英文别名: N1-(1,4-Dioxido-1,2,4-benzotriazin-3-yl)-1,6-hexanediamine；N'-(1,4-dioxido-1,2,4-benzotriazine-1,4-diium-3-yl)hexane-1,6-diamine
• CAS: 676350-16-6
• 化学式: C₁₃H₁₉N₅O₂
• 分子量: 277.326
• InChiKey: CAGCZMACXZPSTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N¹-(1,4-dioxido-1,2,4-benzotriazin-3-yl)-1,6-hexanediamine 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 N¹-(1,4-dioxido-1,2,4-benzotriazin-3-yl)-1,6-hexanediamine dihydrochloride
  参考文献：
  名称：

  [EN] DNA-TARGETED BENZOTRIAZINE 1,4-DIOXIDES AND THEIR USE IN CANCER THERAPY
  [FR] 1,4-DIOXIDES DE BENZOTRIAZINE CIBLEES SUR ADN ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER

  摘要：

  本发明涉及以DNA为靶标的1,2,4-苯并三氮唑-1,4-二氧化物及相关类似物，其制备方法，以及它们作为针对缺氧选择性药物和放射增敏剂在癌症治疗中的应用，无论是单独使用还是与放射线和/或其他抗癌药物结合使用。

  公开号：

  WO2004026846A1
• 作为产物：
  描述：

  3-[(6-t-butyloxycarbamoylhexyl)amino]-1,2,4-benzotriazine 1-oxide 在 盐酸 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 N¹-(1,4-dioxido-1,2,4-benzotriazin-3-yl)-1,6-hexanediamine
  参考文献：
  名称：

  Improved potency of the hypoxic cytotoxin tirapazamine by DNA-targeting

  摘要：

  To improve the potency of the hypoxic cytotoxin tirapazamine (TPZ), we have constructed an analog, SN26955, with the TPZ moiety attached to an acridine chromophore to target the drug to DNA. The underlying reason for this is our previous finding that the hypoxic cytotoxicity of TPZ is a result of its ability to produce DNA double-strand breaks, whereas many of the toxicities of the drug in clinical use are likely the result of its metabolism in the cytoplasm and effects on mitochondria. We found that the DNA-targeted TPZ analog was more potent than TPZ in killing hypoxic cells by 1-2 orders of magnitude, yet it retained the hypoxic selectivity for cell killing of TPZ. We show that SN26955 is only active in producing DNA damage when it is enzymatically reduced while bound to, or in close association with, the DNA. We also show that it has a different cofactor dependence than TPZ for reduction leading to DNA double-strand breaks, suggesting the involvement of a different reductase for production of the lethal lesion than for TPZ. These results show the promise of DNA-targeting of TPZ to produce a DNA compound with greater clinical efficacy than TPZ itself. (C) 2003 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0006-2952(03)00199-0

文献信息

• Dna-targeted benzotriazine 1,4-dioxides and their use in cancer therapy
  申请人：Brown Martin J.

  公开号：US20070191372A1

  公开（公告）日：2007-08-16

  The present invention relates to DNA-targeted 1,2,4-benzotriazine-1,4-dioxides and 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.

  本发明涉及以DNA为靶点的1,2,4-苯并三氮唑-1,4-二氧化物及其相关类似物，其制备方法以及它们作为低氧选择性药物和放射增敏剂在癌症治疗中的使用，可以单独使用或与放射线和/或其他抗癌药物结合使用。