benzyl 1-(4-(2-ethoxy-2-oxoethoxy)benzyl)-1H-indole-6-carboxylate | 1310744-80-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: benzyl 1-(4-(2-ethoxy-2-oxoethoxy)benzyl)-1H-indole-6-carboxylate
• 英文别名: Benzyl 1-[[4-(2-ethoxy-2-oxoethoxy)phenyl]methyl]indole-6-carboxylate
• CAS: 1310744-80-9
• 化学式: C₂₇H₂₅NO₅
• 分子量: 443.499
• InChiKey: TZXFLMMRNQMSCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  66.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 1-(4-(2-ethoxy-2-oxoethoxy)benzyl)-1H-indole-6-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 22.25h， 生成 (R)-2-(1-(4-(carboxymethoxy)benzyl)-1H-indole-6-carboxamido)pentanedioic acid
  参考文献：
  名称：

  Structure-Based Design of a New Series of d-Glutamic Acid Based Inhibitors of Bacterial UDP-N-acetylmuramoyl-l-alanine:d-glutamate Ligase (MurD)

  摘要：

  MurD ligase is one of the key enzymes participating in the intracellular steps of peptidoglycan biosynthesis and constitutes a viable target in the search for novel antibacterial drugs to combat bacterial drug-resistance. We have designed, synthesized, and evaluated a new series of D-glutamic acid-based Escherichia colt MurD inhibitors incorporating the 5-benzylidenethiazolidin-4-one scaffold. The crystal structure of 16 in the MurD active site has provided a good starting point for the design of structurally optimized inhibitors 73-75 endowed with improved MurD inhibitory potency (IC50 between 3 and 7 mu M). Inhibitors 74 and 75 showed weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis. Compounds 73-75, with IC50 values in the low micromolar range, represent the most potent D-Glu-based MurD inhibitors reported to date.

  DOI：

  10.1021/jm2002525
• 作为产物：
  描述：

  2-(4-(羟基甲基)苯氧基)乙酸乙酯 在 氯化亚砜 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 benzyl 1-(4-(2-ethoxy-2-oxoethoxy)benzyl)-1H-indole-6-carboxylate
  参考文献：
  名称：

  Structure-Based Design of a New Series of d-Glutamic Acid Based Inhibitors of Bacterial UDP-N-acetylmuramoyl-l-alanine:d-glutamate Ligase (MurD)

  摘要：

  MurD ligase is one of the key enzymes participating in the intracellular steps of peptidoglycan biosynthesis and constitutes a viable target in the search for novel antibacterial drugs to combat bacterial drug-resistance. We have designed, synthesized, and evaluated a new series of D-glutamic acid-based Escherichia colt MurD inhibitors incorporating the 5-benzylidenethiazolidin-4-one scaffold. The crystal structure of 16 in the MurD active site has provided a good starting point for the design of structurally optimized inhibitors 73-75 endowed with improved MurD inhibitory potency (IC50 between 3 and 7 mu M). Inhibitors 74 and 75 showed weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis. Compounds 73-75, with IC50 values in the low micromolar range, represent the most potent D-Glu-based MurD inhibitors reported to date.

  DOI：

  10.1021/jm2002525

文献信息

• Structure-Based Design of a New Series of <scp>d</scp>-Glutamic Acid Based Inhibitors of Bacterial UDP-<i>N</i>-acetylmuramoyl-<scp>l</scp>-alanine:<scp>d</scp>-glutamate Ligase (MurD)
  作者：Tihomir Tomašić、Nace Zidar、Roman Šink、Andreja Kovač、Didier Blanot、Carlos Contreras-Martel、Andréa Dessen、Manica Müller-Premru、Anamarija Zega、Stanislav Gobec、Danijel Kikelj、Lucija Peterlin Mašič

  DOI：10.1021/jm2002525

  日期：2011.7.14

  MurD ligase is one of the key enzymes participating in the intracellular steps of peptidoglycan biosynthesis and constitutes a viable target in the search for novel antibacterial drugs to combat bacterial drug-resistance. We have designed, synthesized, and evaluated a new series of D-glutamic acid-based Escherichia colt MurD inhibitors incorporating the 5-benzylidenethiazolidin-4-one scaffold. The crystal structure of 16 in the MurD active site has provided a good starting point for the design of structurally optimized inhibitors 73-75 endowed with improved MurD inhibitory potency (IC50 between 3 and 7 mu M). Inhibitors 74 and 75 showed weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis. Compounds 73-75, with IC50 values in the low micromolar range, represent the most potent D-Glu-based MurD inhibitors reported to date.