[2-[(3-Carbamoyl-2,4-difluorophenoxy)methyl]-4-(4-chlorophenyl)-1,3-oxazol-5-yl]methyl acetate | 1531650-02-8

• 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-[(3-Carbamoyl-2,4-difluorophenoxy)methyl]-4-(4-chlorophenyl)-1,3-oxazol-5-yl]methyl acetate
• CAS: 1531650-02-8
• 化学式: C₂₀H₁₅ClF₂N₂O₅
• 分子量: 436.799
• InChiKey: NCDLAXKHYHTZSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [2-[(3-Carbamoyl-2,4-difluorophenoxy)methyl]-4-(4-chlorophenyl)-1,3-oxazol-5-yl]methyl acetate 在 甲醇 、 potassium carbonate 作用下， 反应 1.0h， 生成 3-[[4-(4-Chlorophenyl)-5-(hydroxymethyl)-1,3-oxazol-2-yl]methoxy]-2,6-difluorobenzamide
  参考文献：
  名称：

  Design, synthesis and structure–activity relationships of substituted oxazole–benzamide antibacterial inhibitors of FtsZ

  摘要：

  The design, synthesis and structure-activity relationships of a series of oxazole-benzamide inhibitors of the essential bacterial cell division protein FtsZ are described. Compounds had potent anti-staphylococcal activity and inhibited the cytokinesis of the clinically-significant bacterial pathogen Staphylococcus aureus. Selected analogues possessing a 5-halo oxazole also inhibited a strain of S. aureus harbouring the glycine-to-alanine amino acid substitution at residue 196 of FtsZ which conferred resistance to previously reported inhibitors in the series. Substitutions to the pseudo-benzylic carbon of the scaffold improved the pharmacokinetic properties by increasing metabolic stability and provided a mechanism for creating pro-drugs. Combining multiple substitutions based on the findings reported in this study has provided small-molecule inhibitors of FtsZ with enhanced in vitro and in vivo antibacterial efficacy. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.002
• 作为产物：
  描述：

  2,6-difluoro-3-methoxybenzamide 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 [2-[(3-Carbamoyl-2,4-difluorophenoxy)methyl]-4-(4-chlorophenyl)-1,3-oxazol-5-yl]methyl acetate
  参考文献：
  名称：

  Design, synthesis and structure–activity relationships of substituted oxazole–benzamide antibacterial inhibitors of FtsZ

  摘要：

  The design, synthesis and structure-activity relationships of a series of oxazole-benzamide inhibitors of the essential bacterial cell division protein FtsZ are described. Compounds had potent anti-staphylococcal activity and inhibited the cytokinesis of the clinically-significant bacterial pathogen Staphylococcus aureus. Selected analogues possessing a 5-halo oxazole also inhibited a strain of S. aureus harbouring the glycine-to-alanine amino acid substitution at residue 196 of FtsZ which conferred resistance to previously reported inhibitors in the series. Substitutions to the pseudo-benzylic carbon of the scaffold improved the pharmacokinetic properties by increasing metabolic stability and provided a mechanism for creating pro-drugs. Combining multiple substitutions based on the findings reported in this study has provided small-molecule inhibitors of FtsZ with enhanced in vitro and in vivo antibacterial efficacy. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.002