3-allyl-6-methyl-1,2,4-benzotriazine 1-oxide | 763131-78-8

• 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-allyl-6-methyl-1,2,4-benzotriazine 1-oxide
• 英文别名: 6-methyl-1-oxido-3-prop-2-enyl-1,2,4-benzotriazin-1-ium
• CAS: 763131-78-8
• 化学式: C₁₁H₁₁N₃O
• 分子量: 201.228
• InChiKey: NNJFARBVIKINCS-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：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 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-allyl-6-methyl-1,2,4-benzotriazine 1-oxide 在 臭氧 、 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 乙醇 为溶剂， 反应 1.5h， 以68%的产率得到2-(6-methyl-1-oxido-1,2,4-benzotriazin-3-yl)ethanol
  参考文献：
  名称：

  Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments

  摘要：

  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。

  公开号：

  EP1468688A2
• 作为产物：
  描述：

  烯丙基三丁基锡 、 3-chloro-6-methyl-1,2,4-benzotriazin 1-oxide 在 四(三苯基膦)钯 氮 、 EtOAc pet. ether 、 ethyl acetate dichloromethane 作用下， 反应 6.0h， 以to give alkene 80 (0.97 g, 74%) as a white solid, mp (EtOAc/pet. ether) 65-67° C., 1H NMR δ 8.32 (d, J=8.8 Hz, 1H, H-8), 7.76 (d, J=1.7 Hz, 1H, H-5), 7.50 (dd, J=8.8, 1.7 Hz, 1H, H-7), 6.13-6.21 (m, 1H, H-2′), 5.30 (dq, J=17.0, 1.5 Hz, 1H, H-3′), 5.22 (dq, J=10.1, 1.5 Hz, 1H, H-3′), 3.76 (dq, J=6.9, 1.5 Hz, 2H, H-1′), 2.58 (s, 3H, CH3)的产率得到3-allyl-6-methyl-1,2,4-benzotriazine 1-oxide
  参考文献：
  名称：

  Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments

  摘要：

  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-氧化物和一种或多种苯并噁唑1,4-二氧化物，用于癌症治疗。本发明还提供了一系列新型的1,2,4-苯并噁唑单N-氧化物和相关类似物。这些可用作现有抗癌药物和癌症治疗的细胞毒性增强剂。

  公开号：

  US20040192686A1

文献信息

• Hypoxia-Selective 3-Alkyl 1,2,4-Benzotriazine 1,4-Dioxides: The Influence of Hydrogen Bond Donors on Extravascular Transport and Antitumor Activity
  作者：Michael P. Hay、Karin Pchalek、Frederik B. Pruijn、Kevin O. Hicks、Bronwyn G. Siim、Robert F. Anderson、Sujata S. Shinde、Victoria Phillips、William A. Denny、William R. Wilson

  DOI：10.1021/jm701037w

  日期：2007.12.27

  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.