5-(5-氯-2-甲氧基苯基)-1,3,4-恶二唑-2-胺 | 1016686-46-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 5-(5-氯-2-甲氧基苯基)-1,3,4-恶二唑-2-胺
• 英文名称: 5-(5-Chloro-2-methoxyphenyl)-1,3,4-oxadiazol-2-amine
• CAS: 1016686-46-6
• 化学式: C₉H₈ClN₃O₂
• mdl: MFCD09807184
• 分子量: 225.634
• InChiKey: CMKALBAFLIKUDV-UHFFFAOYSA-N

物化性质

• 沸点：
  417.5±55.0 °C(Predicted)
• 密度：
  1.391±0.06 g/cm3(Predicted)

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：
  0.111
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  对三氟甲硫基苯甲酸 、 5-(5-氯-2-甲氧基苯基)-1,3,4-恶二唑-2-胺 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以24%的产率得到N-(5-(5-chloro-2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)-4-((trifluoromethyl)thio)benzamide
  参考文献：
  名称：

  Ultrapotent Inhibitor of Clostridioides difficile Growth, Which Suppresses Recurrence In Vivo

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.0c01198
• 作为产物：
  描述：

  5-氯-2-甲氧基苯甲醛 在 溴 、 sodium acetate 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 反应 1.5h， 生成 5-(5-氯-2-甲氧基苯基)-1,3,4-恶二唑-2-胺
  参考文献：
  名称：

  Ultrapotent Inhibitor of Clostridioides difficile Growth, Which Suppresses Recurrence In Vivo

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.0c01198

文献信息

• 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.