3-氨基-5-(3,4-二氯苯基)噻吩-2-羧酸 | 649757-55-1

• 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-(3,4-二氯苯基)噻吩-2-羧酸
• 英文名称: 3-Amino-5-(3,4-dichlorophenyl)thiophene-2-carboxylic acid
• 英文别名: 3-amino-5-(3,4-dichlorophenyl)thiophene-2-carboxylic acid
• CAS: 649757-55-1
• 化学式: C₁₁H₇Cl₂NO₂S
• mdl: MFCD25860557
• 分子量: 288.154
• InChiKey: HYSQTYSYSMOAPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  17
• 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-(3,4-二氯苯基)噻吩-2-羧酸 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 2.0h， 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
• 作为产物：
  描述：

  methyl 3-amino-5-(3,4-dichlorophenyl)-2-thiophenecarboxylate 在 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 生成 3-氨基-5-(3,4-二氯苯基)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

• 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.