2-([1,1'-biphenyl]-4-ylcarboxamido)-5-bromobenzoic acid

• 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: 2-([1,1'-biphenyl]-4-ylcarboxamido)-5-bromobenzoic acid
• 英文别名: 2-[(1,1'-biphenyl-4-ylcarbonyl)amino]-5-bromobenzoic acid；2-[(Biphenyl-4-ylcarbonyl)amino]-5-bromobenzoic acid；5-bromo-2-[(4-phenylbenzoyl)amino]benzoic acid
• 化学式: C₂₀H₁₄BrNO₃
• 分子量: 396.24
• InChiKey: HQRXUHNDNXQYCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 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：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  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

文献信息

• Antibacterial agents
  申请人：Thorarensen Atli

  公开号：US20050113450A1

  公开（公告）日：2005-05-26

  The present invention relates to antibacterial agents that are useful for sterilization, sanitation, antisepsis, and disinfection

  本发明涉及用于杀菌、卫生、消毒和消毒的抗菌剂。
• US7429677B2
  申请人：——

  公开号：US7429677B2

  公开（公告）日：2008-09-30
• 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.