5-(3’,4’-dichlorophenyl)-3-[(N-phenylamino)carbonylamino]thiophen-2-carboxylic acid | 1294482-07-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(3’,4’-dichlorophenyl)-3-[(N-phenylamino)carbonylamino]thiophen-2-carboxylic acid
• 英文别名: 5-(3,4-Dichlorophenyl)-3-(phenylcarbamoylamino)thiophene-2-carboxylic acid；5-(3,4-dichlorophenyl)-3-(phenylcarbamoylamino)thiophene-2-carboxylic acid
• CAS: 1294482-07-7
• 化学式: C₁₈H₁₂Cl₂N₂O₃S
• 分子量: 407.277
• InChiKey: CSQJZRZMNNKABQ-UHFFFAOYSA-N

物化性质

• 沸点：
  512.8±50.0 °C(Predicted)
• 密度：
  1.560±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二氯苯乙酮 在 甲醇 、 sodium 、 potassium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 6.75h， 生成 5-(3’,4’-dichlorophenyl)-3-[(N-phenylamino)carbonylamino]thiophen-2-carboxylic acid
  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

• 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.