3,5-dibromo-N-phenylbenzamide | 1070240-91-3

• 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: 3,5-dibromo-N-phenylbenzamide
• CAS: 1070240-91-3
• 化学式: C₁₃H₉Br₂NO
• 分子量: 355.029
• InChiKey: GPTQJKRCZSLCPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 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：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3,5-二溴苯甲酸 在 吡啶 、 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 3,5-dibromo-N-phenylbenzamide
  参考文献：
  名称：

  Hydroxybiphenylamide GroEL/ES Inhibitors Are Potent Antibacterials against Planktonic and Biofilm Forms of Staphylococcus aureus

  摘要：

  We recently reported the identification of a GroEL/ES inhibitor (1, N-(4-(benzo[d]thiazol-2-ylthio)-3-chlorophenyl)-3,5-dibromo-2-hydroxybenzamide) that exhibited in vitro antibacterial effects against Staphylococcus aureus comparable to vancomycin, an antibiotic of last resort. To follow up, we have synthesized 43 compound 1 analogs to determine the most effective functional groups of the scaffold for inhibiting GroEL/ES and killing bacteria. Our results identified that the benzothiazole and hydroxyl groups are important for inhibiting GroEL/ES-mediated folding functions, with the hydroxyl essential for antibacterial effects. Several analogs exhibited >50-fold selectivity indices between antibacterial efficacy and cytotoxicity to human liver and kidney cells in cell culture. We found that MRSA was not able to easily generate acute resistance to lead inhibitors in a gain-of-resistance assay and that lead inhibitors were able to permeate through established S. aureus biofilms and maintain their bactericidal effects.

  DOI：

  10.1021/acs.jmedchem.8b01293

文献信息

• [EN] COMPOUNDS AND METHODS OF INHIBITING BACTERIAL CHAPERONIN SYSTEMS<br/>[FR] COMPOSÉS ET MÉTHODES D'INHIBITION DE SYSTÈMES DE CHAPERONINE BACTÉRIENNE
  申请人：UNIV INDIANA TRUSTEES

  公开号：WO2020092947A1

  公开（公告）日：2020-05-07

  The present disclosure relates to novel compounds and methods of killing or inhibiting the growth of bacteria. In some embodiments, a method of killing or inhibiting the growth of bacteria is provided. The method comprises administering a compound of formula I or a pharmaceutically acceptable salt thereof to bacteria. In some embodiments, a method of killing or inhibiting the growth of bacteria is provided. The method comprises administering an anthelmintic to bacteria.

  本公开涉及新化合物和杀灭或抑制细菌生长的方法。在某些实施方式中，提供了一种杀灭或抑制细菌生长的方法。该方法包括向细菌施用式I的化合物或其药学上可接受的盐。在某些实施方式中，提供了一种杀灭或抑制细菌生长的方法。该方法包括向细菌施用驱虫药。
• Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies
  作者：Steven M. Johnson、Stephen Connelly、Ian A. Wilson、Jeffery W. Kelly

  DOI：10.1021/jm800435s

  日期：2008.10.23

  To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. Herein, we evaluated 40 bisaryl molecules based on 10 unique linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3). Coconsideration of amyloid inhibition and ex vivo plasma TTR binding selectivity data reveal that direct connection of the two aryls or linkage through nonpolar E-olefin or -CH 2CH 2- substructures generates the most potent and selective TTR amyloidogenesis inhibitors exhibiting minimal undesirable binding to the thyroid hormone nuclear receptor or the COX-1 enzyme. Five high-resolution TTR.inhibitor crystal structures (1.4-1.8 A) provide insight into why such linkers afford inhibitors with greater potency and selectivity.
• INHIBITION OF BACTERIAL CHAPERONIN SYSTEMS
  申请人：THE TRUSTEES OF INDIANA UNIVERSITY

  公开号：US20210395210A1

  公开（公告）日：2021-12-23

  The present disclosure relates to novel compounds and methods of killing or inhibiting the growth of bacteria. In some embodiments, a method of killing or inhibiting the growth of bacteria is provided. The method comprises administering a compound of formula I or a pharmaceutically acceptable salt thereof to bacteria. In some embodiments, a method of killing or inhibiting the growth of bacteria is provided. The method comprises administering an anthelmintic to bacteria.
• Hydroxybiphenylamide GroEL/ES Inhibitors Are Potent Antibacterials against Planktonic and Biofilm Forms of <i>Staphylococcus aureus</i>
  作者：Trent Kunkle、Sanofar Abdeen、Nilshad Salim、Anne-Marie Ray、Mckayla Stevens、Andrew J. Ambrose、José Victorino、Yangshin Park、Quyen Q. Hoang、Eli Chapman、Steven M. Johnson

  DOI：10.1021/acs.jmedchem.8b01293

  日期：2018.12.13

  We recently reported the identification of a GroEL/ES inhibitor (1, N-(4-(benzo[d]thiazol-2-ylthio)-3-chlorophenyl)-3,5-dibromo-2-hydroxybenzamide) that exhibited in vitro antibacterial effects against Staphylococcus aureus comparable to vancomycin, an antibiotic of last resort. To follow up, we have synthesized 43 compound 1 analogs to determine the most effective functional groups of the scaffold for inhibiting GroEL/ES and killing bacteria. Our results identified that the benzothiazole and hydroxyl groups are important for inhibiting GroEL/ES-mediated folding functions, with the hydroxyl essential for antibacterial effects. Several analogs exhibited >50-fold selectivity indices between antibacterial efficacy and cytotoxicity to human liver and kidney cells in cell culture. We found that MRSA was not able to easily generate acute resistance to lead inhibitors in a gain-of-resistance assay and that lead inhibitors were able to permeate through established S. aureus biofilms and maintain their bactericidal effects.