2-cyclohexyl-6-(4-fluorophenoxy)-5-(4-methylbenzamido)-1H-benzo[d]imidazole | 1448875-52-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-cyclohexyl-6-(4-fluorophenoxy)-5-(4-methylbenzamido)-1H-benzo[d]imidazole
• 英文别名: N-[2-cyclohexyl-6-(4-fluorophenoxy)-1H-benzimidazol-5-yl]-4-methyl-benzamide；N-[2-cyclohexyl-6-(4-fluorophenoxy)-3H-benzimidazol-5-yl]-4-methylbenzamide
• CAS: 1448875-52-2
• 化学式: C₂₇H₂₆FN₃O₂
• 分子量: 443.521
• InChiKey: ZNLSXPAHZCQBSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  67
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4-二硝基-5-氟苯胺 在 吡啶 、 potassium carbonate 、 tin(ll) chloride 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 33.0h， 生成 2-cyclohexyl-6-(4-fluorophenoxy)-5-(4-methylbenzamido)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents

  摘要：

  Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 mu g/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 mu g/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the K-d of 5a with Mtb-FtsZ was determined to be 1.32 mu M. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.035

文献信息

• [EN] BENZIMIDAZOLES AND USES THEREOF<br/>[FR] BENZIMIDAZOLES ET LEURS UTILISATIONS
  申请人：UNIV NEW YORK STATE RES FOUND

  公开号：WO2013116823A1

  公开（公告）日：2013-08-08

  The present invention relates to novel 2,5,6-benzimidazole derivatives of formula I and pharmaceutically acceptable salts thereof. Another aspect of the invention relates to methods of treating a patient infected by Mycobacterium tuberculosis or Mycobacteriumavium complex by administering to the patient a 2,5,6- benzimidazole derivative or a pharmaceutically acceptable salt thereof.

  本发明涉及公式I的新颖2,5,6-苯并咪唑衍生物及其药学上可接受的盐。发明的另一个方面涉及通过向患有结核分枝杆菌或分枝杆菌复合物感染的患者施用2,5,6-苯并咪唑衍生物或其药学上可接受的盐来治疗患者的方法。
• Methods for in vitro—in vivo efficacy determination
  申请人：COLORADO STATE UNIVERSITY RESEARCH FOUNDATION

  公开号：US10287617B2

  公开（公告）日：2019-05-14

  The invention provides methods for determining and evaluating the in vitro-in vivo activity relationship of the efficacy of families of compounds for infectious diseases such as tuberculosis. The validity of the methods can be confirmed by evaluation of the compounds in animal models, for example, in murine models of tuberculosis. Examples of families of antibacterial compounds that can be evaluated for in vivo efficacy using the in vitro methods described herein include benzimidazoles, pyridopyrazines, pteridines, diphenyl ethers, beta-lactams, PBP inhibitors, and compounds that are non-ribonucleic acid and protein synthesis inhibitors. The methods can be used to evaluate classes of small molecule compounds and inhibitors that may be effective against any bacterial pathogen. The methods aid the identification of compounds, such as various benzimidazoles, with modes of action having activity against clinical isolates, as well as non-replicating persistent bacilli, which can therefore enhance current clinical therapeutic regimens.

  本发明提供了确定和评估化合物家族对传染性疾病（如结核病）疗效的体外-体内活性关系的方法。这些方法的有效性可以通过在动物模型中，例如在结核病小鼠模型中对化合物进行评估来证实。可使用本文所述体外方法评估体内疗效的抗菌化合物家族包括苯并咪唑类、吡啶并嗪类、蝶啶类、二苯醚类、β-内酰胺类、PBP 抑制剂以及非核糖核酸和蛋白质合成抑制剂化合物。这些方法可用于评估可能对任何细菌病原体有效的小分子化合物和抑制剂类别。这些方法有助于鉴定对临床分离菌和非复制持久性杆菌具有活性的化合物，如各种苯并咪唑类化合物，从而改进目前的临床治疗方案。
• METHODS FOR IMPROVED IN VITRO - IN VIVO EFFICACY DETERMINATION
  申请人：COLORADO STATE UNIVERSITY RESEARCH FOUNDATION

  公开号：US20180087085A9

  公开（公告）日：2018-03-29

  The invention provides methods for determining and evaluating the in vitro-in vivo activity relationship of the efficacy of families of compounds for infectious diseases such as tuberculosis. The validity of the methods can be confirmed by evaluation of the compounds in animal models, for example, in murine models of tuberculosis. Examples of families of antibacterial compounds that can be evaluated for in vivo efficacy using the in vitro methods described herein include benzimidazoles, pyridopyrazines, pteridines, diphenyl ethers, beta-lactams, PBP inhibitors, and compounds that are non-ribonucleic acid and protein synthesis inhibitors. The methods can be used to evaluate classes of small molecule compounds and inhibitors that may be effective against any bacterial pathogen. The methods aid the identification of compounds, such as various benzimidazoles, with modes of action having activity against clinical isolates, as well as non-replicating persistent bacilli, which can therefore enhance current clinical therapeutic regimens.
• Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents
  作者：Bora Park、Divya Awasthi、Soumya R. Chowdhury、Eduard H. Melief、Kunal Kumar、Susan E. Knudson、Richard A. Slayden、Iwao Ojima

  DOI：10.1016/j.bmc.2014.03.035

  日期：2014.5

  Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 mu g/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 mu g/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the K-d of 5a with Mtb-FtsZ was determined to be 1.32 mu M. (C) 2014 Elsevier Ltd. All rights reserved.