2-cyclohexyl-6-(N,N-diethylamino)-5-(4-ethylbenzamido)-1Hbenzo[d]imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-cyclohexyl-6-(N,N-diethylamino)-5-(4-ethylbenzamido)-1Hbenzo[d]imidazole
• 英文别名: N-[2-cyclohexyl-6-(diethylamino)-1H-benzimidazol-5-yl]-4-ethyl-benzamide；N-[2-cyclohexyl-6-(diethylamino)-3H-benzimidazol-5-yl]-4-ethylbenzamide
• 化学式: C₂₆H₃₄N₄O
• 分子量: 418.582
• InChiKey: GBDQWPGWVWZXGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  61
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,4-二硝基-5-氟苯胺 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 tin(II) chloride dihdyrate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成 2-cyclohexyl-6-(N,N-diethylamino)-5-(4-ethylbenzamido)-1Hbenzo[d]imidazole
  参考文献：
  名称：

  SAR Studies on Trisubstituted Benzimidazoles as Inhibitors of Mtb FtsZ for the Development of Novel Antitubercular Agents

  摘要：

  FtsZ, an essential protein for bacterial cell division, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of two lead 2,5,6-trisubstituted benzimidazoles, 1 and 2, targeting Mtb-FtsZ in our previous study, an extensive SAR study for optimization of these lead compounds was performed through systematic modification of the 5 and 6 positions. This study has successfully led to the discovery of a highly potent advanced lead 5f (MIC = 0.06 mu g/mL) and several other compounds with comparable potencies. These advanced lead compounds possess a dimethylamino group at the 6 position. The functional groups at the 5 position exhibit substantial effects on the antibacterial activity as well. In vitro experiments such as the FtsZ polymerization inhibitory assay and TEM analysis of Mtb-FtsZ treated with 5f and others indicate that Mtb-FtsZ is the molecular target for their antibacterial activity.

  DOI：

  10.1021/jm401468w

文献信息

• 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.
• SAR Studies on Trisubstituted Benzimidazoles as Inhibitors of <i>Mtb</i> FtsZ for the Development of Novel Antitubercular Agents
  作者：Divya Awasthi、Kunal Kumar、Susan E. Knudson、Richard A. Slayden、Iwao Ojima

  DOI：10.1021/jm401468w

  日期：2013.12.12

  FtsZ, an essential protein for bacterial cell division, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of two lead 2,5,6-trisubstituted benzimidazoles, 1 and 2, targeting Mtb-FtsZ in our previous study, an extensive SAR study for optimization of these lead compounds was performed through systematic modification of the 5 and 6 positions. This study has successfully led to the discovery of a highly potent advanced lead 5f (MIC = 0.06 mu g/mL) and several other compounds with comparable potencies. These advanced lead compounds possess a dimethylamino group at the 6 position. The functional groups at the 5 position exhibit substantial effects on the antibacterial activity as well. In vitro experiments such as the FtsZ polymerization inhibitory assay and TEM analysis of Mtb-FtsZ treated with 5f and others indicate that Mtb-FtsZ is the molecular target for their antibacterial activity.