3-氨基-5-(4-溴苯基)噻吩-2-羧酸 | 649757-51-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 3-氨基-5-(4-溴苯基)噻吩-2-羧酸
• 英文名称: 3-amino-5-(4’-bromophenyl)thiophene-2-carboxylic acid
• 英文别名: 3-Amino-5-(4-bromophenyl)thiophene-2-carboxylic acid
• CAS: 649757-51-7
• 化学式: C₁₁H₈BrNO₂S
• 分子量: 298.16
• InChiKey: BBNPJAUKYYWMIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基-5-(4-溴苯基)噻吩-2-羧酸 在 三乙胺 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 2.5h， 生成 (S)-3-(3’’-(1-carboxy-2-phenylethyl)ureido)-5-(4’-bromophenyl)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：

  甲基3-氨基-5-(4-溴苯基)-2-噻吩羧酸酯 在 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 3.0h， 生成 3-氨基-5-(4-溴苯基)噻吩-2-羧酸
  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

文献信息

• PHOSPHOTHIOPHENE AND PHOSPHOTHIAZOLE HCV POLYMERASE INHIBITORS
  申请人：Dousson Cyril

  公开号：US20100233123A1

  公开（公告）日：2010-09-16

  Provided herein are phosphothiophene and phosphothiazole compounds, for example, of any of Formulae I, IA, IIA, IIIA, IVA, VA, VIA, VIIA, IB, IIB, IIIB, IVB, VB, VIIB and VIIB disclosed herein, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host infected with HCV.

  本文提供了磷硫杂苯和磷硫杂唑化合物，例如公式I、IA、IIA、IIIA、IVA、VA、VIA、VIIA、IB、IIB、IIIB、IVB、VB、VIIB和VIIB中的任何一种，以及包含这些化合物的制药组合物和其制备方法。同时提供了这些化合物用于治疗HCV感染的方法，该方法适用于HCV感染的宿主。
• Phosphothiophene and phosphothiazole HCV polymerase inhibitors
  申请人：Idenix Pharmaceuticals, Inc.

  公开号：US08193372B2

  公开（公告）日：2012-06-05

  Provided herein are phosphothiophene and phosphothiazole compounds, for example, of any of Formulae I, IA, IIA, IIIA, IVA, VA, VIA, VIIA, IB, IIB, IIIB, IVB, VB, VIB and VIIB disclosed herein, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host infected with HCV.

  本文提供了磷硫吡嗪和磷硫唑化合物，例如在本文中披露的任何I、IA、IIA、IIIA、IVA、VA、VIA、VIIA、IB、IIB、IIIB、IVB、VB、VIB和VIIB式中的化合物，以及包含这些化合物的制药组合物和制备它们的过程。还提供了它们用于治疗HCV感染的方法，该方法适用于HCV感染的宿主。
• [EN] PHOSPHOTHIOPHENE AND PHOSPHOTHIAZOLE HCV POLYMERASE INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHOTHIOPHÈNE ET PHOSPHOTHIAZOLE VHC POLYMÉRASE
  申请人：IDENIX PHARMACEUTICALS INC

  公开号：WO2010101967A3

  公开（公告）日：2010-11-11
• Novel small molecule inhibitors targeting the “switch region” of bacterial RNAP: Structure-based optimization of a virtual screening hit
  作者：J. Henning Sahner、Matthias Groh、Matthias Negri、Jörg Haupenthal、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2013.04.060

  日期：2013.7

  Rising resistance against current antibiotics necessitates the development of antibacterial agents with alternative targets. The "switch region" of RNA polymerase (RNAP), addressed by the myxopyronins, could be such a novel target site. Based on a hit candidate discovered by virtual screening, a small library of 5-phenyl-3-ureidothiophene-2-carboxylic acids was synthesized resulting in compounds with increased RNAP inhibition. Hansch analysis revealed pi (lipophilicity constant) and sigma (Hammet substituent constant) of the substituents at the 5-phenyl moiety to be crucial for activity. The binding mode was proven by the targeted introduction of a moiety mimicking the enecarbamate side chain of myxopyronin into the hit compound, accompanied by enhanced RNAP inhibitory potency. The new compounds displayed good antibacterial activities against Gram positive bacteria and Gram negative Escherichia coli TolC and a reduced resistance frequency compared to the established antibiotic rifampicin. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Combining in Silico and Biophysical Methods for the Development of Pseudomonas aeruginosa Quorum Sensing Inhibitors: An Alternative Approach for Structure-Based Drug Design
  作者：J. Henning Sahner、Christian Brengel、Michael P. Storz、Matthias Groh、Alberto Plaza、Rolf Müller、Rolf W. Hartmann

  DOI：10.1021/jm401102e

  日期：2013.11.14

  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.