cesium (R)-2-(3-carbamoyl-2,4-difluorophenoxy)-3-hydroxy-propionate | 1403884-04-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: cesium (R)-2-(3-carbamoyl-2,4-difluorophenoxy)-3-hydroxy-propionate
• 英文别名: Cesium (R)-2-(3-carbamoyl-2,4-difluorophenoxy)-3-hydroxypropionate；cesium;(2R)-2-(3-carbamoyl-2,4-difluorophenoxy)-3-hydroxypropanoate
• CAS: 1403884-04-7
• 化学式: C₁₀H₈F₂NO₅*Cs
• 分子量: 393.079
• InChiKey: QUTSDTSABBWDDU-FYZOBXCZSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.44
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  cesium (R)-2-(3-carbamoyl-2,4-difluorophenoxy)-3-hydroxy-propionate 在 乙酰胺 、 三氟化硼乙醚 作用下， 以 N,N-二甲基甲酰胺 、 xylenes 为溶剂， 反应 3.0h， 生成 2,6-difluoro-3-{(R)-2-hydroxy-1-[4-(4-trifluoromethylphenyl)oxazol-2-yl]ethoxy}benzamide
  参考文献：
  名称：

  [EN] AROMATIC AMIDES AND USES THEREOF
  [FR] AMIDES AROMATIQUES ET LEURS UTILISATIONS

  摘要：

  本发明提供了化合物的结构式(I)：以及它们的盐、消旋体、异构体、对映异构体、立体异构体、水合物、溶剂合物、N-氧化物、药学上可接受的衍生物或前药。还提供了这些化合物作为抗菌剂的用途，包括它们的组合物和制造过程。

  公开号：

  WO2012142671A1
• 作为产物：
  描述：

  2,6-二氟-3-羟基苯甲酰胺 在 10 wt% Pd(OH)2 on carbon 、 水 、 氢气 、 caesium carbonate 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 55.0 ℃ 、101.33 kPa 条件下， 反应 53.0h， 生成 cesium (R)-2-(3-carbamoyl-2,4-difluorophenoxy)-3-hydroxy-propionate
  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

• [EN] AROMATIC AMIDES AND USES THEREOF<br/>[FR] AMIDES AROMATIQUES ET LEURS UTILISATIONS
  申请人：BIOTA SCIENT MANAGEMENT

  公开号：WO2012142671A1

  公开（公告）日：2012-10-26

  The present invention provides compounds of Formula (I): and salts, racemates, isomers, diastereoisomers, enantiomers, hydrates, solvates, N-oxides, pharmaceutically acceptable derivatives or prodrugs thereof. Also provided the use of these compounds as antibacterials, compositions comprising them and processes for their manufacture.

  本发明提供了化合物的结构式(I)：以及它们的盐、消旋体、异构体、对映异构体、立体异构体、水合物、溶剂合物、N-氧化物、药学上可接受的衍生物或前药。还提供了这些化合物作为抗菌剂的用途，包括它们的组合物和制造过程。
• AROMATIC AMIDES AND USES THEREOF
  申请人：Haydon David John

  公开号：US20140135332A1

  公开（公告）日：2014-05-15

  The present invention provides compounds of Formula (I): and salts, racemates, isomers, diastereoisomers, enantiomers, hydrates, solvates, N-oxides, pharmaceutically acceptable derivatives or prodrugs thereof. Also provided the use of these compounds as antibacterials, compositions comprising them and processes for their manufacture.

  本发明提供了式（I）的化合物及其盐、外消旋体、异构体、对映异构体、水合物、溶剂化物、N-氧化物、药学上可接受的衍生物或前药。同时提供了这些化合物作为抗菌剂的用途、包含它们的组合物以及它们的制造过程。
• 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.