1-{4-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)pyrimidin-2-yl}azetidin-3-ol

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-{4-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)pyrimidin-2-yl}azetidin-3-ol
• 英文别名: 1-[4-[4-Methyl-2-(4-phenylphenyl)-1,3-thiazol-5-yl]pyrimidin-2-yl]azetidin-3-ol；1-[4-[4-methyl-2-(4-phenylphenyl)-1,3-thiazol-5-yl]pyrimidin-2-yl]azetidin-3-ol
• 化学式: C₂₃H₂₀N₄OS
• 分子量: 400.504
• InChiKey: LKWYBWALGXSDNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)ethanone 在 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 1-{4-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)pyrimidin-2-yl}azetidin-3-ol
  参考文献：
  名称：

  Investigating the Antibacterial Activity of Biphenylthiazoles against Methicillin- and Vancomycin-Resistant Staphylococcus aureus (MRSA and VRSA)

  摘要：

  Phenylthiazoles were reported previously as a new scaffold with antibacterial activity against an array of multidrug-resistant staphylococci. However, their promising antibacterial activity was hampered in large part by their short half-life due to excessive hepatic clearance. Close inspection of the structure-activity-relationships (SARs) of the phenylthiazoles revealed two important structural features necessary for antibacterial activity (a nitrogenous and a lipophilic component). Incorporating the nitrogenous part within a pyrimidine ring resulted in analogues with a prolonged half-life, while the biphenyl moiety revealed the most potent analogue 1b. In this study, advantageous moieties have been combined to generate a new hybrid scaffold of 5-pyrimidinylbiphenylthiazole with the objective of enhancing both anti-MRSA activity and drug-like properties. Among the 37 tested biphenylthiazoles, piperazinyl-containing derivatives 10, 30, and 36 were the most potent analogues with MIC values as low as 0.39 mu g/mL. Additionally, 36 exhibited significant improvement in stability to hepatic metabolism.

  DOI：

  10.1021/acs.jmedchem.7b00392

文献信息

• Investigating the Antibacterial Activity of Biphenylthiazoles against Methicillin- and Vancomycin-Resistant <i>Staphylococcus aureus</i> (MRSA and VRSA)
  作者：Mohamed Hagras、Haroon Mohammad、Mohamed S. Mandour、Youssef A. Hegazy、Adel Ghiaty、Mohamed N. Seleem、Abdelrahman S. Mayhoub

  DOI：10.1021/acs.jmedchem.7b00392

  日期：2017.5.11

  Phenylthiazoles were reported previously as a new scaffold with antibacterial activity against an array of multidrug-resistant staphylococci. However, their promising antibacterial activity was hampered in large part by their short half-life due to excessive hepatic clearance. Close inspection of the structure-activity-relationships (SARs) of the phenylthiazoles revealed two important structural features necessary for antibacterial activity (a nitrogenous and a lipophilic component). Incorporating the nitrogenous part within a pyrimidine ring resulted in analogues with a prolonged half-life, while the biphenyl moiety revealed the most potent analogue 1b. In this study, advantageous moieties have been combined to generate a new hybrid scaffold of 5-pyrimidinylbiphenylthiazole with the objective of enhancing both anti-MRSA activity and drug-like properties. Among the 37 tested biphenylthiazoles, piperazinyl-containing derivatives 10, 30, and 36 were the most potent analogues with MIC values as low as 0.39 mu g/mL. Additionally, 36 exhibited significant improvement in stability to hepatic metabolism.