5-(3-(trifluoromethoxy)phenyl)-1,3,4-oxadiazol-2-amine | 1450828-17-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(3-(trifluoromethoxy)phenyl)-1,3,4-oxadiazol-2-amine
• 英文别名: 5-[3-(Trifluoromethoxy)phenyl]-1,3,4-oxadiazole-2-amine；5-[3-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-amine
• CAS: 1450828-17-7
• 化学式: C₉H₆F₃N₃O₂
• 分子量: 245.161
• InChiKey: CTXAKNKEPDTZNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-(3-(trifluoromethoxy)phenyl)-1,3,4-oxadiazol-2-amine 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 24.0h， 生成 2-(2-(3,4-dimethoxyphenyl)-5,7-dimethoxy-4-oxo-4H-chromen-3-yloxy)-N-(5-(3-(trifluoromethoxy)phenyl)-1,3,4-oxadiazol-2-yl)acetamide
  参考文献：
  名称：

  含有1,3,4-恶二唑部分的新型2-苯基-4H-色酮衍生物的合成、端粒酶抑制和抗癌活性

  摘要：

  摘要 根据先前的研究，制备了 66 种含有酰胺和 1,3,4-恶二唑部分的 2-苯基-4H-色酮衍生物作为潜在的端粒酶抑制剂。结果显示大多数标题化合物对端粒酶表现出显着的抑制活性。其中，一些化合物表现出最有效的端粒酶抑制活性（IC 50 < 1 µM），明显优于星形孢菌素（IC 50 = 6.41 µM）。此外，总结了清晰的构效关系，表明甲氧基的取代以及苯环上取代基的位置、类型和数量对端粒酶活性有显着影响。其中，化合物A33对端粒酶有显着的抑制作用。流式细胞仪分析表明，化合物A33可以将MGC-803细胞周期阻滞在G2/M期，并以浓度依赖性方式诱导细胞凋亡。同时，Western blotting 显示该化合物可以降低作为端粒酶片段的dyskerin 的表达。

  DOI：

  10.1080/14756366.2020.1864630
• 作为产物：
  描述：

  2-(3-(trifluoromethoxy)benzoyl)hydrazinecarbothioamide 在 1,3-二溴-5,5-二甲基海因 、 potassium iodide 、 sodium hydroxide 作用下， 以 水 、 异丙醇 、 乙腈 为溶剂， 反应 1.0h， 以20%的产率得到5-(3-(trifluoromethoxy)phenyl)-1,3,4-oxadiazol-2-amine
  参考文献：
  名称：

  Discovery and Biophysical Characterization of 2-Amino-oxadiazoles as Novel Antagonists of PqsR, an Important Regulator of Pseudomonas aeruginosa Virulence

  摘要：

  The human pathogen Pseudomonas aeruginosa employs alkyl quinolones for cell-to-cell communication. The Pseudomonas quinolone signal (PQS) regulates various virulence factors via interaction with the transcriptional regulator PqsR. Therefore, we consider the development of PqsR antagonists a novel strategy to limit the pathogenicity of P. aeruginosa. A fragment identification approach using surface plasmon resonance screening led to the discovery of chemically diverse PqsR ligands. The optimization of the most promising hit (5) resulted in the oxadiazole-2-amine 37 showing pure antagonistic activity in Escherichia coli (EC50 = 7.5 mu M) and P. aeruginosa (EC50 = 38.5 mu M) reporter gene assays. 37 was able to diminish the production of the PQS precursor HHQ in a PqsH-deficient P. aeruginosa mutant The level of the major virulence factor pyocyanin was significantly reduced in wild-type P. aeruginosa. In addition, site-directed mutagenesis in combination with isothermal titration calorimetry and NMR INPHARMA experiments revealed that the identified ligands bind to the same site of PqsR by adopting different binding modes. These findings will be utilized in a future fragment growing approach aiming at novel therapeutic options for the treatment of P. aeruginosa infections.

  DOI：

  10.1021/jm400830r

文献信息

• Discovery and Biophysical Characterization of 2-Amino-oxadiazoles as Novel Antagonists of PqsR, an Important Regulator of Pseudomonas aeruginosa Virulence
  作者：Michael Zender、Tobias Klein、Claudia Henn、Benjamin Kirsch、Christine K. Maurer、Dagmar Kail、Christiane Ritter、Olan Dolezal、Anke Steinbach、Rolf W. Hartmann

  DOI：10.1021/jm400830r

  日期：2013.9.12

  The human pathogen Pseudomonas aeruginosa employs alkyl quinolones for cell-to-cell communication. The Pseudomonas quinolone signal (PQS) regulates various virulence factors via interaction with the transcriptional regulator PqsR. Therefore, we consider the development of PqsR antagonists a novel strategy to limit the pathogenicity of P. aeruginosa. A fragment identification approach using surface plasmon resonance screening led to the discovery of chemically diverse PqsR ligands. The optimization of the most promising hit (5) resulted in the oxadiazole-2-amine 37 showing pure antagonistic activity in Escherichia coli (EC50 = 7.5 mu M) and P. aeruginosa (EC50 = 38.5 mu M) reporter gene assays. 37 was able to diminish the production of the PQS precursor HHQ in a PqsH-deficient P. aeruginosa mutant The level of the major virulence factor pyocyanin was significantly reduced in wild-type P. aeruginosa. In addition, site-directed mutagenesis in combination with isothermal titration calorimetry and NMR INPHARMA experiments revealed that the identified ligands bind to the same site of PqsR by adopting different binding modes. These findings will be utilized in a future fragment growing approach aiming at novel therapeutic options for the treatment of P. aeruginosa infections.
• Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety
  作者：Xu Han、Yun Long Yu、Duo Ma、Zhao Yan Zhang、Xin Hua Liu

  DOI：10.1080/14756366.2020.1864630

  日期：2021.1.1

  66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC50 < 1 µM), which was significantly superior to the staurosporine (IC50

  摘要 根据先前的研究，制备了 66 种含有酰胺和 1,3,4-恶二唑部分的 2-苯基-4H-色酮衍生物作为潜在的端粒酶抑制剂。结果显示大多数标题化合物对端粒酶表现出显着的抑制活性。其中，一些化合物表现出最有效的端粒酶抑制活性（IC 50 < 1 µM），明显优于星形孢菌素（IC 50 = 6.41 µM）。此外，总结了清晰的构效关系，表明甲氧基的取代以及苯环上取代基的位置、类型和数量对端粒酶活性有显着影响。其中，化合物A33对端粒酶有显着的抑制作用。流式细胞仪分析表明，化合物A33可以将MGC-803细胞周期阻滞在G2/M期，并以浓度依赖性方式诱导细胞凋亡。同时，Western blotting 显示该化合物可以降低作为端粒酶片段的dyskerin 的表达。