methyl 2-([1,1'-biphenyl]-4-ylcarboxamido)-5-bromobenzoate | 307540-02-9

• 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: methyl 2-([1,1'-biphenyl]-4-ylcarboxamido)-5-bromobenzoate
• 英文别名: Methyl 5-bromo-2-[(4-phenylbenzoyl)amino]benzoate
• CAS: 307540-02-9
• 化学式: C₂₁H₁₆BrNO₃
• 分子量: 410.267
• InChiKey: NWTQYYPBUXWHOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-([1,1'-biphenyl]-4-ylcarboxamido)-5-bromobenzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.0h， 以31%的产率得到2-([1,1'-biphenyl]-4-ylcarboxamido)-5-bromobenzoic acid
  参考文献：
  名称：

  Discovery of Novel Bacterial RNA Polymerase Inhibitors: Pharmacophore-Based Virtual Screening and Hit Optimization

  摘要：

  The bacterial RNA polymerase (RNAP) is a validated target for broad spectrum antibiotics. However, the efficiency of drugs is reduced by resistance. To discover novel RNAP inhibitors, a pharmacophore based on the alignment of described inhibitors was used for virtual screening. In an optimization process of hit compounds, novel derivatives with improved in vitro potency were discovered. Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between sigma(70) and the RNAP core enzyme. Besides of reducing RNA formation, the inhibitors were shown to interfere with bacterial lipid biosynthesis. The compounds were active against Gram-positive pathogens and revealed significantly lower resistance frequencies rifampicin.

  DOI：

  10.1021/jm400485e
• 作为产物：
  描述：

  2-氨基-5-溴苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 methyl 2-([1,1'-biphenyl]-4-ylcarboxamido)-5-bromobenzoate
  参考文献：
  名称：

  Discovery of Novel Bacterial RNA Polymerase Inhibitors: Pharmacophore-Based Virtual Screening and Hit Optimization

  摘要：

  The bacterial RNA polymerase (RNAP) is a validated target for broad spectrum antibiotics. However, the efficiency of drugs is reduced by resistance. To discover novel RNAP inhibitors, a pharmacophore based on the alignment of described inhibitors was used for virtual screening. In an optimization process of hit compounds, novel derivatives with improved in vitro potency were discovered. Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between sigma(70) and the RNAP core enzyme. Besides of reducing RNA formation, the inhibitors were shown to interfere with bacterial lipid biosynthesis. The compounds were active against Gram-positive pathogens and revealed significantly lower resistance frequencies rifampicin.

  DOI：

  10.1021/jm400485e

文献信息

• Discovery of Novel Bacterial RNA Polymerase Inhibitors: Pharmacophore-Based Virtual Screening and Hit Optimization
  作者：Stefan Hinsberger、Kristina Hüsecken、Matthias Groh、Matthias Negri、Jörg Haupenthal、Rolf W. Hartmann

  DOI：10.1021/jm400485e

  日期：2013.11.14

  The bacterial RNA polymerase (RNAP) is a validated target for broad spectrum antibiotics. However, the efficiency of drugs is reduced by resistance. To discover novel RNAP inhibitors, a pharmacophore based on the alignment of described inhibitors was used for virtual screening. In an optimization process of hit compounds, novel derivatives with improved in vitro potency were discovered. Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between sigma(70) and the RNAP core enzyme. Besides of reducing RNA formation, the inhibitors were shown to interfere with bacterial lipid biosynthesis. The compounds were active against Gram-positive pathogens and revealed significantly lower resistance frequencies rifampicin.
• 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.