(S)-3-(3’’-(1-carboxy-2-phenylethyl)ureido)-5-(4’-methoxyphenyl)thiophene-2-carboxylic acid | 1472069-75-2

• 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: (S)-3-(3’’-(1-carboxy-2-phenylethyl)ureido)-5-(4’-methoxyphenyl)thiophene-2-carboxylic acid
• 英文别名: 3-[[(1S)-1-carboxy-2-phenylethyl]carbamoylamino]-5-(4-methoxyphenyl)thiophene-2-carboxylic acid
• CAS: 1472069-75-2
• 化学式: C₂₂H₂₀N₂O₆S
• 分子量: 440.477
• InChiKey: FARUJXRRLJYHNN-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-(3’’-(1-carboxy-2-phenylethyl)ureido)-5-(4’-methoxyphenyl)thiophene-2-carboxylic acid 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 (S)-3-(3-(1-carboxy-2-phenylethyl)ureido)-5-(4-hydroxyphenyl)thiophene-2-carboxylic acid
  参考文献：
  名称：

  Exploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa

  摘要：

  Pseudomonas aeruginosa employs a quorum sensing (QS) communication system that makes use of small diffusible molecules. Among other effects, the QS system coordinates the formation of biofilm which decisively contributes to difficulties in the therapy of Pseudomonas infections. The present work deals with the structure-activity exploration of ureidothiophene-2-carboxylic acids as inhibitors of PqsD, a key enzyme in the biosynthetic pathway of signal molecules in the Pseudomonas QS system. We describe an improvement of the inhibitory activity by successfully combining features from two different PqsD inhibitor classes. Furthermore the functional groups, which are responsible for the inhibitory potency, were identified. Moreover, the inability of the new inhibitors, to prevent signal molecule formation in whole cell assays, is discussed. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.007
• 作为产物：
  描述：

  3-氨基-5-(4-甲氧基苯基)噻吩-2-羧酸 在 水 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.5h， 生成 (S)-3-(3’’-(1-carboxy-2-phenylethyl)ureido)-5-(4’-methoxyphenyl)thiophene-2-carboxylic acid
  参考文献：
  名称：

  Combining in Silico and Biophysical Methods for the Development of Pseudomonas aeruginosa Quorum Sensing Inhibitors: An Alternative Approach for Structure-Based Drug Design

  摘要：

  The present work deals with the optimization of an inhibitor of PqsD, an enzyme essential for Pseudomonas aeruginosa quorum sensing apparatus. Molecular docking studies, supported by biophysical methods (surface plasmon resonance, isothermal titration calorimetry, saturation transfer difference NMR), were used to illuminate the binding mode of the 5-aryl-ureidothiophene-2-carboxylic acids. Enabled to make profound predictions, structure-based optimization led to increased inhibitory potency. Finally a covalent inhibitor was obtained. Binding to the active site was confirmed by LC-ESI-MS and MALDI-TOF-MS experiments. Following this rational approach, potent PqsD inhibitors were efficiently developed within a short period of time. This example shows that a combination and careful application of in silico and biophysical methods represents a powerful complement to cocrystallography.

  DOI：

  10.1021/jm401102e