thiazol-5-yl | 1531650-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: thiazol-5-yl
• 英文别名: 2,6-Difluoro-3-[[4-[4-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazol-2-yl]methoxy]benzamide；2,6-difluoro-3-[[4-[4-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazol-2-yl]methoxy]benzamide
• CAS: 1531650-64-2
• 化学式: C₁₉H₁₀F₈N₂O₄
• 分子量: 482.287
• InChiKey: NKKWKBFXSXUMBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  87.6
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  2-methyl-4-(4-(trifluoromethoxy)phenyl)oxazole 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 偶氮二异丁腈 、 N-(2-羟基丙基)甲基丙烯酰胺 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 thiazol-5-yl
  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

文献信息

• COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
  申请人：TAXIS Pharmaceuticals, Inc.

  公开号：US20170305943A1

  公开（公告）日：2017-10-26

  Compounds and methods are provided for treating bacterial infections.
• Design, synthesis and structure–activity relationships of substituted oxazole–benzamide antibacterial inhibitors of FtsZ
  作者：Neil R. Stokes、Nicola Baker、James M. Bennett、Pramod K. Chauhan、Ian Collins、David T. Davies、Maruti Gavade、Dushyant Kumar、Paul Lancett、Rebecca Macdonald、Leanne MacLeod、Anu Mahajan、Jeffrey P. Mitchell、Narendra Nayal、Yashodanand Nandan Nayal、Gary R.W. Pitt、Mahipal Singh、Anju Yadav、Anil Srivastava、Lloyd G. Czaplewski、David J. Haydon

  DOI：10.1016/j.bmcl.2013.11.002

  日期：2014.1

  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.