Walrycin B; 1,6-二甲基-3-[4-(三氟甲基)苯基]嘧啶并[5,4-e]-1,2,4-三嗪-5,7(1H,6H)-二酮 | 878419-78-4

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: Walrycin B; 1,6-二甲基-3-[4-(三氟甲基)苯基]嘧啶并[5,4-e]-1,2,4-三嗪-5,7(1H,6H)-二酮
• 中文别名: WalrycinB;1,6-二甲基-3-[4-(三氟甲基)苯基]嘧啶并[5,4-e]-1,2,4-三嗪-5,7(1H,6H)-二酮；1,6-二甲基-3-[4-(三氟甲基)苯基]嘧啶并[5,4-E]-1,2,4-三嗪-5,7(1H,6H)-二酮；WalrycinB抑制剂
• 英文名称: 1,6-dimethyl-3-[4-(trifluoromethyl)phenyl]pyrimido[5,4-e][1,2,4]triazine-5,7-dione
• 英文别名: walrycin B
• CAS: 878419-78-4
• 化学式: C₁₄H₁₀F₃N₅O₂
• 分子量: 337.261
• InChiKey: XRVMPTWWKLKLPB-UHFFFAOYSA-N

物化性质

• 沸点：
  383.1±52.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO 中≥33.7 mg/mL；不溶于水；不溶于乙醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  77.7
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P264,P270,P301+P312,P330
• 危险性描述：
  H302,H315,H320,H335

制备方法与用途

生物活性 Walrycin B 是一种抗菌化合物，有效抑制了 WalR 反应调节剂。其靶点如下：

Target	Value
WalR

反应信息

• 作为产物：
  描述：

  6-氯-3-甲基尿嘧啶 在 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 19.34h， 生成 Walrycin B; 1,6-二甲基-3-[4-(三氟甲基)苯基]嘧啶并[5,4-e]-1,2,4-三嗪-5,7(1H,6H)-二酮
  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

• 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
• [EN] INHIBITORS OF CYSTATHIONINE BETA SYNTHASE TO REDUCE THE NEUROTOXIC OVERPRODUCTION OF ENDOGENOUS HYDROGEN SULFIDE<br/>[FR] INHIBITEURS DE CYSTATHIONINE BÊTA-SYNTHASE POUR RÉDUIRE LA SURPRODUCTION NEUROTOXIQUE DE SULFURE D'HYDROGÈNE ENDOGÈNE
  申请人：FOND JEROME LEJEUNE

  公开号：WO2010072807A2

  公开（公告）日：2010-07-01

  The invention is directed to inhibitors of cystathionine beta synthase which, among other biochemical effects, allow reduction of the neurotoxic overproduction of endogenous hydrogen sulphide. These compounds and pharmaceutical compositions containing them are useful for the prevention and treatment of neurotoxic and cognitive disorders such as cognitive disorders in Down syndrome. The invention also relates to methods for preventing or treating neurotoxic and cognitive disorders including cognitive disorders in Down Syndrome.