2-(4-hydroxyphenyl)-4-methy-5-acetylthiazole | 867330-01-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-hydroxyphenyl)-4-methy-5-acetylthiazole
• 英文别名: 1-[2-(4-Hydroxyphenyl)-4-methyl-1,3-thiazol-5-yl]ethanone；1-[2-(4-hydroxyphenyl)-4-methyl-1,3-thiazol-5-yl]ethanone
• CAS: 867330-01-6
• 化学式: C₁₂H₁₁NO₂S
• mdl: MFCD07339544
• 分子量: 233.291
• InChiKey: CVFSPXYVIUTMQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-hydroxyphenyl)-4-methy-5-acetylthiazole 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 1-(4-methyl-2-(4-(3-(3-methylpiperidin-1-yl)propoxy)phenyl)thiazol-5-yl)ethan-1-one
  参考文献：
  名称：

  Modifying the lipophilic part of phenylthiazole antibiotics to control their drug-likeness

  摘要：

  Compounds with high lipophilic properties are often associated with bad physicochemical properties, triggering many off-targets, and less likely to pass clinical trials. Two metabolically stable phenylthiazole antibiotic scaffolds having notable high lipophilic characters, one with alkoxy side chain and the other one with alkynyl moiety, were derivatized by inserting a cyclic amine at the lipophilic tail with the objective of improving physicochemical properties and the overall pharmacokinetic behavior. Only alkynyl derivatives with 4- or 5-membered rings showed remarkable antibacterial activity. The azetidine-containing compound 8 was the most effective and it revealed a potent antibacterial effect against 15 multi-drug resistant (MDR)-Gram positive pathogens including Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis and enterococci. Compound 8 was also highly effective in clearing 99.7% of the intracellular methicillin-resistant S. aureus (MRSA) harbored inside macrophages. In addition to the remarkable enhancement in aqueous solubility, the in vivo pharmacokinetic study in rats indicated that compound B can penetrate gut cells and reach plasma at a therapeutic concentration within 15 min and maintain effective plasma concentration for around 12 h. Interestingly, the main potential metabolite (compound 9) was also active as an antibacterial agent with potent antibiofilm activity. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111830
• 作为产物：
  描述：

  4-羟基苯甲酰胺 在 劳森试剂 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 11.0h， 生成 2-(4-hydroxyphenyl)-4-methy-5-acetylthiazole
  参考文献：
  名称：

  Phenylthiazole antibiotics: A metabolism-guided approach to overcome short duration of action

  摘要：

  Antibacterial resistance is a pressing global health challenge that necessitates the development of new therapeutic agents. Phenylthiazole antibacterial agents have been extensively studied, by our group, as a potential novel class of antibiotics to circumvent the scourge of antibacterial resistance. Previously, the phenylthiazole lead compound I was shown to possess potent activity against clinical isolates of methicillin-and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA). The promising activity of this novel class of antibiotics is hampered by their short half-life due to rapid hepatic metabolism. In the present study, a metabolic methylene soft spot in the lead 1 was identified and replaced with an oxygen atom. The newly developed phenylthiazoles, with alkoxy side chains, demonstrate high metabolic stability (t(1/2) > 4 h), while maintaining their potent anti-MRSA activity. Furthermore, compound 5p demonstrated a selective advantage over vancomycin with its ability to kill intracellular MRSA.(C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.11.042

文献信息

• Phenylthiazole antibiotics: A metabolism-guided approach to overcome short duration of action
  作者：Eman Yahia、Haroon Mohammad、Tamer M. Abdelghany、Eman Fayed、Mohamed N. Seleem、Abdelrahman S. Mayhoub

  DOI：10.1016/j.ejmech.2016.11.042

  日期：2017.1

  Antibacterial resistance is a pressing global health challenge that necessitates the development of new therapeutic agents. Phenylthiazole antibacterial agents have been extensively studied, by our group, as a potential novel class of antibiotics to circumvent the scourge of antibacterial resistance. Previously, the phenylthiazole lead compound I was shown to possess potent activity against clinical isolates of methicillin-and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA). The promising activity of this novel class of antibiotics is hampered by their short half-life due to rapid hepatic metabolism. In the present study, a metabolic methylene soft spot in the lead 1 was identified and replaced with an oxygen atom. The newly developed phenylthiazoles, with alkoxy side chains, demonstrate high metabolic stability (t(1/2) > 4 h), while maintaining their potent anti-MRSA activity. Furthermore, compound 5p demonstrated a selective advantage over vancomycin with its ability to kill intracellular MRSA.(C) 2016 Elsevier Masson SAS. All rights reserved.
• Modifying the lipophilic part of phenylthiazole antibiotics to control their drug-likeness
  作者：Yomna Hosny、Nader S. Abutaleb、Mariam Omara、Marwa Alhashimi、Mohamed M. Elsebaei、Heba S. Elzahabi、Mohamed N. Seleem、Abdelrahman S. Mayhoub

  DOI：10.1016/j.ejmech.2019.111830

  日期：2020.1

  Compounds with high lipophilic properties are often associated with bad physicochemical properties, triggering many off-targets, and less likely to pass clinical trials. Two metabolically stable phenylthiazole antibiotic scaffolds having notable high lipophilic characters, one with alkoxy side chain and the other one with alkynyl moiety, were derivatized by inserting a cyclic amine at the lipophilic tail with the objective of improving physicochemical properties and the overall pharmacokinetic behavior. Only alkynyl derivatives with 4- or 5-membered rings showed remarkable antibacterial activity. The azetidine-containing compound 8 was the most effective and it revealed a potent antibacterial effect against 15 multi-drug resistant (MDR)-Gram positive pathogens including Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis and enterococci. Compound 8 was also highly effective in clearing 99.7% of the intracellular methicillin-resistant S. aureus (MRSA) harbored inside macrophages. In addition to the remarkable enhancement in aqueous solubility, the in vivo pharmacokinetic study in rats indicated that compound B can penetrate gut cells and reach plasma at a therapeutic concentration within 15 min and maintain effective plasma concentration for around 12 h. Interestingly, the main potential metabolite (compound 9) was also active as an antibacterial agent with potent antibiofilm activity. (C) 2019 Elsevier Masson SAS. All rights reserved.