1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dione | 878419-18-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dione
• 英文别名: 1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione
• CAS: 878419-18-2
• 化学式: C₁₀H₁₃N₅O₂
• 分子量: 235.246
• InChiKey: LKBYYUZEKINDPS-UHFFFAOYSA-N

物化性质

• 沸点：
  316.1±25.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)
• 溶解度：
  >35.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  77.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dione 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 24.0h， 以46%的产率得到1,5-dimethyl-3-propyl-1H-imidazo[4,5-e][1,2,4]triazin-6(5H)-one
  参考文献：
  名称：

  6-氮杂嘌呤类化合物通过弓形黄素（7-氮杂吡啶）的转化简便合成

  摘要：

  - 本文描述了通过处理毒黄素可靠而简便地合成 6-氮杂嘌呤 (1,5-dimethyl-1H-imidazo[4,5-e][1,2,4]triazin-6(5H)-ones) (7-azapteridines) 与 10% 氢氧化钠水溶液在 5-25 °C 下进行苯甲酸型重排，然后通过空气进行脱羧和氧化。此外，在 10% 乙醇氢氧化钠中加热 6-氮杂嘌呤，得到相应的 1,2,4-三嗪-5,6(1H,4H)-二酮，这是由 6-氮杂嘌呤的咪唑环裂变引起的。

  DOI：

  10.3987/com-08-s(f)111
• 作为产物：
  描述：

  3-甲基-6-(1-甲基肼基)-2,4(1H,3H)-嘧啶二酮 在 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 19.17h， 生成 1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dione
  参考文献：
  名称：

  Toxoflavins and Deazaflavins as the First Reported Selective Small Molecule Inhibitors of Tyrosyl-DNA Phosphodiesterase II

  摘要：

  The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAP.) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.

  DOI：

  10.1021/jm400568p

文献信息

• The Facile Synthesis of 6-Azapurines by Transformation of Toxoflavins (7-Azapteridines)
  作者：Tomohisa Nagamatsu、Jun Ma、Fumio Yoneda

  DOI：10.3987/com-08-s(f)111

  日期：——

  - This paper describes a reliable and facile synthesis of 6-azapurines (1,5-dimethyl-1H-imidazo[4,5-e][1,2,4]triazin-6(5H)-ones) by treatment of toxoflavins (7-azapteridines) with 10% aqueous sodium hydroxide at 5-25 °C along with a benzilic acid type rearrangement, followed by decarboxylation and oxidation by air. Furthermore, heating the 6-azapurines in 10% ethanolic sodium hydroxides afforded the

  - 本文描述了通过处理毒黄素可靠而简便地合成 6-氮杂嘌呤 (1,5-dimethyl-1H-imidazo[4,5-e][1,2,4]triazin-6(5H)-ones) (7-azapteridines) 与 10% 氢氧化钠水溶液在 5-25 °C 下进行苯甲酸型重排，然后通过空气进行脱羧和氧化。此外，在 10% 乙醇氢氧化钠中加热 6-氮杂嘌呤，得到相应的 1,2,4-三嗪-5,6(1H,4H)-二酮，这是由 6-氮杂嘌呤的咪唑环裂变引起的。
• Inhibitors of HIV-1 integrase multimerization
  申请人：Institute for Cancer Research

  公开号：US10888564B2

  公开（公告）日：2021-01-12

  The disclosure generally relates to compounds of formulas (I) and (II)7 including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV-1 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

  本公开一般涉及式(I)和(II)7化合物，包括治疗人类免疫缺陷病毒（HIV）感染的组合物和方法。本公开提供了 HIV-1 整合酶的新型抑制剂、含有此类化合物的药物组合物以及使用这些化合物治疗 HIV 感染的方法。
• COMPOUNDS AND METHODS FOR TREATING TUBERCULOSIS INFECTION
  申请人：Wong Chi-Huey

  公开号：US20130158037A1

  公开（公告）日：2013-06-20

  The present invention provides compounds which are potent inhibitors against Lpd activity, PDH activity, and/or the growth of tubercle bacillus , and thus are useful in the treatment of tuberculosis infection and associated conditions. The present invention is further directed to in vitro- and in vzivo-based methods of inhibiting Lpd and/or PDH activity. In certain embodiments, these methods are useful in inhibiting Lpd and/or PDH activity key to a pathogen's survival.
• INHIBITORS OF HIV-1 INTEGRASE MULTIMERIZATION
  申请人：Institute for Cancer Research d/b/a The Research Institute of Fox Chase Cancer Center

  公开号：US20210113570A1

  公开（公告）日：2021-04-22

  The disclosure generally relates to compounds, compositions, and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV-1 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
• US9073941B2
  申请人：——

  公开号：US9073941B2

  公开（公告）日：2015-07-07