1-(4-fluorophenylsulfonamido)-3-morpholinopropan-2-yl dihydrogen phosphate | 1144506-91-1

• 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: 1-(4-fluorophenylsulfonamido)-3-morpholinopropan-2-yl dihydrogen phosphate
• 英文别名: HEA derivative, 7b；[1-[(4-fluorophenyl)sulfonylamino]-3-morpholin-4-ylpropan-2-yl] dihydrogen phosphate
• CAS: 1144506-91-1
• 化学式: C₁₃H₂₀FN₂O₇PS
• 分子量: 398.349
• InChiKey: PQONZGNIVZDUAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  134
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 platinum(IV) oxide 、 氢气 、 溶剂黄146 作用下， 反应 96.0h， 以47%的产率得到1-(4-fluorophenylsulfonamido)-3-morpholinopropan-2-yl phenyl hydrogen phosphate
  参考文献：
  名称：

  Design and synthesis of new hydroxyethylamines as inhibitors of d-alanyl-d-lactate ligase (VanA) and d-alanyl-d-alanine ligase (DdlB)

  摘要：

  The Van enzymes are ATP-dependant ligases responsible for resistance to vancomycin in Staphylococcus aureus and Enteroccoccus species. The de novo molecular design programme SPROUT was used in conjunction with the X-ray crystal structure of Enterococcus faecium D-alanyl-D-lactate ligase (VanA) to design new putative inhibitors based on a hydroxyethylamine template. The two best ranked structures were selected and efficient syntheses developed. The inhibitory activities of these molecules were determined on E. faecium VanA, and due to structural similarity and a common reaction mechanism, also on D-Ala-D-Ala ligase (DdlB) from Escherichia coli. The phosphate group attached to the hydroxyl moiety of the hydroxyethylamine isostere within these systems is essential for their inhibitory activity against both VanA and DdlB. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.034

文献信息

• Phosphorylated hydroxyethylamines as novel inhibitors of the bacterial cell wall biosynthesis enzymes MurC to MurF
  作者：Matej Sova、Andreja Kovač、Samo Turk、Martina Hrast、Didier Blanot、Stanislav Gobec

  DOI：10.1016/j.bioorg.2009.09.001

  日期：2009.12

  Enzymes involved in the biosynthesis of bacterial peptidoglycan represent important targets for development of new antibacterial drugs. Among them, Mur ligases (MurC to MurF) catalyze the formation of the final cytoplasmic precursor UDP-N-acetylmuramyl-pentapeptide from UDP-N-acetylmuramic acid. We present the design, synthesis and biological evaluation of a series of phosphorylated hydroxyethylamines as new type of small-molecule inhibitors of Mur ligases. We show that the phosphate group attached to the hydroxyl moiety of the hydroxyethylamine core is essential for good inhibitory activity. The IC50 values of these inhibitors were in the micromolar range, which makes them a promising starting point for the development of multiple inhibitors of Mur ligases as potential antibacterial agents. In addition, 1-(4-methoxyphenylsulfonamido)-3-morpholinopropan-2-yl dihydrogen phosphate 7a was discovered as one of the best inhibitors of MurE described so far. (C) 2009 Elsevier Inc. All rights reserved.
• Design and synthesis of new hydroxyethylamines as inhibitors of d-alanyl-d-lactate ligase (VanA) and d-alanyl-d-alanine ligase (DdlB)
  作者：Matej Sova、Gašper Čadež、Samo Turk、Vita Majce、Slovenko Polanc、Sarah Batson、Adrian J. Lloyd、David I. Roper、Colin W.G. Fishwick、Stanislav Gobec

  DOI：10.1016/j.bmcl.2009.01.034

  日期：2009.3

  The Van enzymes are ATP-dependant ligases responsible for resistance to vancomycin in Staphylococcus aureus and Enteroccoccus species. The de novo molecular design programme SPROUT was used in conjunction with the X-ray crystal structure of Enterococcus faecium D-alanyl-D-lactate ligase (VanA) to design new putative inhibitors based on a hydroxyethylamine template. The two best ranked structures were selected and efficient syntheses developed. The inhibitory activities of these molecules were determined on E. faecium VanA, and due to structural similarity and a common reaction mechanism, also on D-Ala-D-Ala ligase (DdlB) from Escherichia coli. The phosphate group attached to the hydroxyl moiety of the hydroxyethylamine isostere within these systems is essential for their inhibitory activity against both VanA and DdlB. (C) 2009 Elsevier Ltd. All rights reserved.