3,5-dibromo-N-(3-chlorophenyl)-2-hydroxybenzamide | 6149-61-7

• 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: 3,5-dibromo-N-(3-chlorophenyl)-2-hydroxybenzamide
• CAS: 6149-61-7
• 化学式: C₁₃H₈Br₂ClNO₂
• mdl: MFCD00552937
• 分子量: 405.473
• InChiKey: NOBGQGXPNOIMQT-UHFFFAOYSA-N

物化性质

• 沸点：
  393.3±42.0 °C(Predicted)
• 密度：
  1.921±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  19
• 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：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5-dibromo-N-(3-chlorophenyl)-2-hydroxybenzamide 、 氯甲酸乙酯 以 吡啶 为溶剂， 反应 1.0h， 以81%的产率得到6,8-Dibromo-3-(3-chlorophenyl)-1,3-benzoxazine-2,4-dione
  参考文献：
  名称：

  抗分枝杆菌物质的化学结构与其对非典型菌株的活性之间的关系。第 14 部分：3-Aryl-6,8-dihalo-2H-1,3-benzoxazine-2,4 (3H) -diones

  摘要：

  6,8-二氯-3-苯基-2H-苯并恶嗪-2,4(3H)-二酮的八种衍生物和6,8-二溴-3-苯基-2H-1,3-苯并恶嗪-的九种衍生物苯环上取代的 2,4 (3H)-二酮是通过相应的水杨酰苯胺与氯甲酸乙酯反应制备的。在体外评估了这些化合物对结核分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌的抗分枝杆菌活性。它们的活性随着苯环上取代基的疏水性和吸电子能力的增加而增加。

  DOI：

  10.1002/(sici)1521-4184(199801)331:1<3::aid-ardp3>3.0.co;2-2
• 作为产物：
  描述：

  3,5-Dibromo-2-methoxybenzoyl chloride 在 吡啶 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 90.0h， 生成 3,5-dibromo-N-(3-chlorophenyl)-2-hydroxybenzamide
  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

• 5-Bromo- and 3,5-dibromo-2-hydroxy-N-phenylbenzamides — inhibitors of photosynthesis
  作者：Katarína Kráľová、František Šeršeň、Matúš Peško、Karel Waisser、Lenka Kubicová

  DOI：10.2478/s11696-013-0416-7

  日期：2014.1.1

  5-Bromo-(Br-PBA) and 3,5-dibromo-2-hydroxy-N-phenylbenzamides (Br2-PBA) inhibited photosynthetic electron transport (PET) and their inhibitory efficiency depended on the compound lipophilicity as well as on the electronic properties of the R substituent in the N-phenyl moiety. Br-PBA showed higher PET inhibiting activity than Br2-PBA with the same R substituent. The most effective inhibitors in the tested series were the derivatives with R = 3-F (Br-PBA; IC50 = 4.3 μmol dm−3) and R = 3-Cl (Br2-PBA; IC50 = 8.6 μmol dm−3). Bilinear dependence of the PET inhibiting activity on the lipophilicity of the compounds as well as on the Hammett constant, σ, of the R substituent was observed for both investigated series. Using EPR spectroscopy it was found that the site of action of the tested compounds in the photosynthetic apparatus is situated on the donor side of PS 2, in D· or in the Z·/D· intermediates. Interaction of the studied compounds with chlorophyll a and aromatic amino acids present in the pigment-protein complexes mainly in photosystem 2 was documented by fluorescence spectroscopy.

  摘要：5-溴-(Br-PBA)和3,5-二溴-2-羟基-N-苯基苯甲酰胺（Br2-PBA）抑制了光合作用电子传递（PET），它们的抑制效率取决于化合物的亲脂性以及N-苯基基团中R取代基的电子性质。Br-PBA表现出比具有相同R取代基的Br2-PBA更高的PET抑制活性。在测试系列中，具有R = 3-F（Br-PBA; IC50 = 4.3 μmol dm−3）和R = 3-Cl（Br2-PBA; IC50 = 8.6 μmol dm−3）的衍生物是最有效的抑制剂。对于两个研究系列，观察到了PET抑制活性与化合物的亲脂性以及R取代基的Hammett常数σ之间的双线性依赖关系。使用EPR光谱学发现，测试化合物在光合作用器官中的作用位点位于PS 2的给体侧，在D·或在Z·/D·中间体中。通过荧光光谱学证明了研究化合物与叶绿素a和存在于色素蛋白复合物中的芳香氨基酸的相互作用主要发生在光系统2中。
• [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。
• 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.
• Relationships Between the Chemical Structure of Antimycobacterial Substances and Their Activity Against Atypical Strains. Part 14: 3-Aryl-6,8-dihalogeno-2H-1,3-benzoxazine-2,4(3H)-diones
  作者：Karel Waisser、Jana Hladuvková、Jirí Gregor、Tomáš Rada、Lenka Kubicová、Vera Klimešová、Jarmila Kaustová

  DOI：10.1002/(sici)1521-4184(199801)331:1<3::aid-ardp3>3.0.co;2-2

  日期：1998.1

  6,8‐dibromo‐3‐phenyl‐2H‐1,3‐benzoxazine‐2,4(3H)‐dione, substituted on the phenyl ring, was prepared by the reaction of the corresponding salicylanilides with ethyl chloroformate. The compounds were evaluated in vitro for antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. Their activity increases with increasing hydrophobicity and electron‐withdrawing

  6,8-二氯-3-苯基-2H-苯并恶嗪-2,4(3H)-二酮的八种衍生物和6,8-二溴-3-苯基-2H-1,3-苯并恶嗪-的九种衍生物苯环上取代的 2,4 (3H)-二酮是通过相应的水杨酰苯胺与氯甲酸乙酯反应制备的。在体外评估了这些化合物对结核分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌的抗分枝杆菌活性。它们的活性随着苯环上取代基的疏水性和吸电子能力的增加而增加。
• 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.