3-(1,4-dioxido-1,2,4-benzotriazin-3-yl)propyl trifluoroacetate | 1001430-84-7

• 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: 3-(1,4-dioxido-1,2,4-benzotriazin-3-yl)propyl trifluoroacetate
• CAS: 1001430-84-7
• 化学式: C₁₂H₁₀F₃N₃O₄
• 分子量: 317.224
• InChiKey: UIVATOWTPVJAIJ-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  3-(1,4-dioxido-1,2,4-benzotriazin-3-yl)propyl trifluoroacetate 在 ammonium hydroxide 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以62%的产率得到3-(1-Oxido-4-oxo-1,2,4-benzotriazin-4-ium-3-yl)propan-1-ol
  参考文献：
  名称：

  Hypoxia-Selective 3-Alkyl 1,2,4-Benzotriazine 1,4-Dioxides: The Influence of Hydrogen Bond Donors on Extravascular Transport and Antitumor Activity

  摘要：

  Tirapazamine (TPZ) and related 1,2,4-benzotriazine 1,4 dioxides (BTOs) are selectively toxic under hypoxia, but their ability to kill hypoxic cells in tumors is generally limited by their poor extravascular transport. Here we show that removing hydrogen bond donors by replacing the 3-NH2 group of TPZ with simple alkyl groups increased their tissue diffusion coefficients as measured in multicellular layer cultures. This advantage was largely retained using solubilizing 3-alkylaminoalkyl substituents provided these were sufficiently lipophilic at pH 7.4. The high reduction potentials of such compounds resulted in rates of metabolism too high for optimal penetration into hypoxic tissue, but electron-donating 6- and 7-substituents moderated metabolism. Pharmacokinetic/pharmacodynamic model-guided screening was used to select BTOs with optimal extravascular transport and hypoxic cytotoxicity properties for evaluation against HT29 human tumor xenografts in combination with radiation. This identified four novel 3-alkyl BTOs providing greater clonogenic killing of hypoxic cells than TPZ at equivalent host toxicity, with the 6-morpholinopropyloxy-BTO 22 being 3-fold more active.

  DOI：

  10.1021/jm701037w