(R,Z)-dimethyl 2-(3-((4-methoxy-4-oxo-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenyl)butanamido)methyl)benzamido)pentanedioate | 1310744-94-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R,Z)-dimethyl 2-(3-((4-methoxy-4-oxo-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenyl)butanamido)methyl)benzamido)pentanedioate
• 英文别名: dimethyl (2R)-2-[[3-[[N-(4-methoxy-4-oxobutanoyl)-4-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]anilino]methyl]benzoyl]amino]pentanedioate
• CAS: 1310744-94-5
• 化学式: C₃₀H₃₁N₃O₉S₂
• 分子量: 641.723
• InChiKey: XXXZWIIHSQWYKQ-LEYFIJQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  44
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  215
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (R,Z)-dimethyl 2-(3-((4-methoxy-4-oxo-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenyl)butanamido)methyl)benzamido)pentanedioate 在 lithium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 以23%的产率得到(R,Z)-2-(3-((3-carboxy-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenyl)propanamido)methyl)benzamido)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：

  (5Z)-5-(4-aminobenzylidene)-2-thioxo-1,3-thiazolidin-4-one 在 溶剂黄146 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 45.0h， 生成 (R,Z)-dimethyl 2-(3-((4-methoxy-4-oxo-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenyl)butanamido)methyl)benzamido)pentanedioate
  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.