3-氨基-5-(4-甲氧基苯基)噻吩-2-羧酸 | 649757-53-9

• 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-甲氧基苯基)噻吩-2-羧酸
• 英文名称: 3-amino-5-(4’-methoxyphenyl)thiophene-2-carboxylic acid
• 英文别名: 3-Amino-5-(4-methoxyphenyl)thiophene-2-carboxylic acid
• CAS: 649757-53-9
• 化学式: C₁₂H₁₁NO₃S
• mdl: MFCD12031197
• 分子量: 249.29
• InChiKey: OVZGEYCSYDYAAG-UHFFFAOYSA-N

物化性质

• 熔点：
  142 °C
• 沸点：
  511.0±50.0 °C(Predicted)
• 密度：
  1.362±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  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-carboxyethyl)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
• 作为产物：
  描述：

  对甲氧基苯乙酮 在 甲醇 、 sodium 、 potassium hydroxide 、 三氯氧磷 作用下， 以 甲醇 、 水 为溶剂， 反应 4.75h， 生成 3-氨基-5-(4-甲氧基苯基)噻吩-2-羧酸
  参考文献：
  名称：

  Novel small molecule inhibitors targeting the “switch region” of bacterial RNAP: Structure-based optimization of a virtual screening hit

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2013.04.060

文献信息

• Synthesis of Novel 2-Thienylimino-1,3-thiazolidin-4-ones
  作者：Gilbert Kirsch、Ismail Abdillahi、Germain Revelant、Yazid Datoussaid

  DOI：10.1055/s-0029-1218780

  日期：2010.8

  The preparation of new 2-thienylimino-1,3-thiazolidin-4-ones from 3-aminothiophene-2-carboxylate using an easy four-step procedure is described.

  本文介绍了用 3-氨基噻吩-2-羧酸酯通过简单的四步程序制备新的 2-噻吩亚氨基-1,3-噻唑烷-4-酮的方法。
• Glycogen Phosphorylase Inhibitor Compounds and Pharmaceutical Compositions Thereof
  申请人：Evans Karen

  公开号：US20070249670A1

  公开（公告）日：2007-10-25

  The invention relates to glycogen phosphorylase inhibitor compounds, pharmaceutical compositions of these compounds, methods of treatment using the pharmaceutical compositions to treat diabetes, conditions associated with diabetes, and/or tissue ischemia, including myocardial ischemia, and processes for making the compounds.

  本发明涉及糖原磷酸化酶抑制剂化合物、这些化合物的药物组合物、使用这些药物组合物治疗糖尿病、与糖尿病相关的疾病和/或组织缺血，包括心肌缺血的方法，以及制备这些化合物的过程。
• Exploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa
  作者：J. Henning Sahner、Martin Empting、Ahmed Kamal、Elisabeth Weidel、Matthias Groh、Carsten Börger、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2015.04.007

  日期：2015.5

  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.
• 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.
• Benzamidobenzoic acids as potent PqsD inhibitors for the treatment of Pseudomonas aeruginosa infections
  作者：Stefan Hinsberger、Johannes C. de Jong、Matthias Groh、Jörg Haupenthal、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2014.02.014

  日期：2014.4

  Targeting PqsD is a promising novel approach to disrupt bacterial cell-to-cell-communication in Pseudomonas aeruginosa. In search of selective PqsD inhibitors, two series of benzamidobenzoic acids - one published as RNAP inhibitors and the other as PqsD inhibitors - were investigated for inhibitory activity toward the respective other enzyme. Additionally, novel derivatives were synthesized and biologically evaluated. By this means, the structural features needed for benzamidobenzoic acids to be potent and, most notably, selective PqsD inhibitors were identified. The most interesting compound of this study was the 3-Cl substituted compound 5 which strongly inhibits PqsD (IC50 6.2 mu M) while exhibiting no inhibition of RNAP. (C) 2014 Elsevier Masson SAS. All rights reserved.