6-(4'-bromophenyl)-2,4-dihydro-1H-thieno[3,2-d][1,3]oxazine-2,4-dione | 649757-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 6-(4'-bromophenyl)-2,4-dihydro-1H-thieno[3,2-d][1,3]oxazine-2,4-dione
• 英文别名: 6-(4’-bromophenyl)-2,4-dihydro-1H-thieno[3,2-d][1,3]oxazine-2,4-dione；6-(4-bromophenyl)-2H-thieno[3,2-d][1,3]oxazine-2,4(1H)-dione；6-(4-Bromophenyl)-2H-thieno[3,2-d][1,3]oxazine-2,4(1H)-dione；6-(4-bromophenyl)-1H-thieno[3,2-d][1,3]oxazine-2,4-dione
• CAS: 649757-40-4
• 化学式: C₁₂H₆BrNO₃S
• 分子量: 324.155
• InChiKey: LOPKZWKLIQGTMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4'-bromophenyl)-2,4-dihydro-1H-thieno[3,2-d][1,3]oxazine-2,4-dione 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 生成 3-(3-((S)-1-carboxy-2-phenylethyl)ureido)-5-(4'-(hydroxy(2-nitrophenyl)methyl)-[1,1'-biphenyl]-4-yl)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-(4-Bromophenyl)-3-chloroprop-2-enenitrile 在 sodium 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 6.0h， 生成 6-(4'-bromophenyl)-2,4-dihydro-1H-thieno[3,2-d][1,3]oxazine-2,4-dione
  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

文献信息

• Synthesis and combinatorial approach of the reactivity of 6- and 7-arylthieno[3,2-d][1,3]oxazine-2,4-diones
  作者：François-Xavier Le Foulon、Emmanuelle Braud、Frédéric Fabis、Jean-Charles Lancelot、Sylvain Rault

  DOI：10.1016/j.tet.2003.10.028

  日期：2003.12

  This paper describes a general procedure for the synthesis of new substituted thiaisatoic anhydrides or 6- or 7-aryl-1H-thiéno[3,2-d][1,3]oxazine-2,4-diones 3a–j and 4a–f. They were synthesized in large scale under microwave heating conditions with high yields. The reactivity vs nucleophilic reagents of these compounds was studied and permitted to develop a simple combinatorial procedure to synthesize

  本文描述了合成新的取代硫代硫杂酸酐或6-或7-芳基-1 H-噻吩并[3,2- d ] [1,3]恶嗪-2,4-二酮3a – j和4a的一般程序。 – f。它们在微波加热条件下以高收率大规模合成。研究了这些化合物的亲核试剂的反应性与亲核试剂的关系，并允许开发一种简单的组合方法来合成新的噻吩脲酸7a – j和8a – j库。
• 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.