5-[3-(三氟甲基)苯基]-1,3,4-恶二唑-2-胺 | 5711-64-8

• 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: 5-[3-(三氟甲基)苯基]-1,3,4-恶二唑-2-胺
• 英文名称: 5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-amine
• 英文别名: 5-[3-(Trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-amine
• CAS: 5711-64-8
• 化学式: C₉H₆F₃N₃O
• mdl: MFCD01710639
• 分子量: 229.161
• InChiKey: SFKXKVUEXCFQLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  64.9
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-[3-(三氟甲基)苯基]-1,3,4-恶二唑-2-胺 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-(5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yloxy)-N-(5-(3-(trifluoromethyl)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-(trifluoromethyl)benzoyl)hydrazinecarbothioamide 在 Oxone 、 碘 、 sodium hydroxide 作用下， 以 水 、 异丙醇 为溶剂， 反应 0.5h， 以59%的产率得到5-[3-(三氟甲基)苯基]-1,3,4-恶二唑-2-胺
  参考文献：
  名称：

  A Convenient Synthesis of 5-substituted 2-amino-1,3,4-oxadiazoles from Corresponding Acylthiosemicarbazides Using iodine and Oxone®

  摘要：

  我们开发了一种简便的方法，在 Oxone® 作为大量氧化剂存在的情况下，使用催化量的碘/KI，从相应的酰基硫代氨基甲酰肼合成取代的 2-氨基-1,3,4-恶二唑。这种方法具有反应时间短、底物可变性强的优点，适合快速生产先导优化计划所需的类似物。由于反应条件温和，且使用的试剂在商业上既便宜又安全，因此该方法也可用于大规模合成。

  DOI：

  10.3184/174751912x13551638283701

文献信息

• Antibacterial Small Molecules That Potently Inhibit <i>Staphylococcus aureus</i> Lipoteichoic Acid Biosynthesis
  作者：George A. Naclerio、Caroline W. Karanja、Clement Opoku‐Temeng、Herman O. Sintim

  DOI：10.1002/cmdc.201900053

  日期：2019.5.17

  The rise of antibiotic resistance, especially in Staphylococcus aureus, and the increasing death rate due to multiresistant bacteria have been well documented. The need for new chemical entities and/or the identification of novel targets for antibacterial drug development is high. Lipoteichoic acid (LTA), a membrane-attached anionic polymer, is important for the growth and virulence of many Gram-positive

  抗生素耐药性的上升，特别是在金黄色葡萄球菌中，以及由于多重耐药细菌导致的死亡率增加已得到了充分的证明。对新的化学实体和/或鉴定用于抗菌药物开发的新靶标的需求很高。脂磷壁酸（LTA）是一种附着在膜上的阴离子聚合物，对许多革兰氏阳性细菌的生长和毒力很重要，人们对LTA生物合成抑制剂的发现也很感兴趣。迄今为止，仅描述了少数LTA生物合成抑制剂对金黄色葡萄球菌具有中等（MIC = 5.34μgmL-1）到低（MIC = 1024μgmL-1）的活性。在本文中，我们描述了有效抑制金黄色葡萄球菌LTA生物合成，表现出令人印象深刻的抗菌活性（MIC低至0的新化合物）的鉴定。25μgmL-1）的耐甲氧西林金黄色葡萄球菌（MRSA）。在类似的体外测定条件下，这些化合物的抗MRSA活性比万古霉素高4倍，比利奈唑胺高8倍。
• 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 of 2-Amino-1,3,4-oxadiazoles and 2-Amino-1,3,4-thiadiazoles via Sequential Condensation and I₂-Mediated Oxidative C–O/C–S Bond Formation
  作者：Pengfei Niu、Jinfeng Kang、Xianhai Tian、Lina Song、Hongxu Liu、Jie Wu、Wenquan Yu、Junbiao Chang

  DOI：10.1021/jo502518c

  日期：2015.1.16

  2-Amino-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles were synthesized via condensation of semicarbazide/thiosemicarbazide and the corresponding aldehydes followed by I-2-mediated oxidative C-O/C-S bond formation. This transition-metal-free sequential synthesis process is compatible with aromatic, aliphatic, and cinnamic aldehydes, providing facile access to a variety of diazole derivatives bearing a 2-amino substituent in an efficient and scalable fashion.
• Ultrapotent Inhibitor of <i>Clostridioides difficile</i> Growth, Which Suppresses Recurrence <i>In Vivo</i>
  作者：George A. Naclerio、Nader S. Abutaleb、Daoyi Li、Mohamed N. Seleem、Herman O. Sintim

  DOI：10.1021/acs.jmedchem.0c01198

  日期：2020.10.22

  Clostridioides difficile is the leading cause of healthcare-associated infection in the U.S. and considered an urgent threat by the Centers for Disease Control and Prevention (CDC). Only two antibiotics, vancomycin and fidaxomicin, are FDA-approved for the treatment of C. difficile infection (CDI), but these therapies still suffer from high treatment failure and recurrence. Therefore, new chemical entities to treat CDI are needed. Trifluoromethylthio-containing N-(1,3,4-oxadiazol-2-yl)benzamides displayed very potent activities [sub-μg/mL minimum inhibitory concentration (MIC) values] against Gram-positive bacteria. Here, we report remarkable antibacterial activity enhancement via halogen substitutions, which afforded new anti-C. difficile agents with ultrapotent activities [MICs as low as 0.003 μg/mL (0.007 μM)] that surpassed the activity of vancomycin against C. difficile clinical isolates. The most promising compound in the series, HSGN-218, is nontoxic to mammalian colon cells and is gut-restrictive. In addition, HSGN-218 protected mice from CDI recurrence. Not only does this work provide a potential clinical lead for the development of C. difficile therapeutics but also highlights dramatic drug potency enhancement via halogen substitution.
• 신규 옥사다이아졸 유도체 및 이의 용도
  申请人：(주)셀로스바이오텍

  公开号：KR102422881B1

  公开（公告）日：2022-07-20

  본 발명은 옥사다이아졸 유도체 및 이를 포함하는 NADPH 산화효소(NOX) 관련 질환 예방 또는 치료용 조성물에 관한 것으로, NOX 억제에 대한 우수한 작용을 통해 NADPH 산화효소(NOX) 와 관련된 질환의 치료에 이용될 수 있다.