5-(4-butylurea)-2-cyclohexyl-6-pyrrolidinyl-1H-benzo[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: 5-(4-butylurea)-2-cyclohexyl-6-pyrrolidinyl-1H-benzo[d]imidazole
• 英文别名: 1-butyl-3-(2-cyclohexyl-6-pyrrolidin-1-yl-1H-benzimidazol-5-yl)urea；1-butyl-3-(2-cyclohexyl-6-pyrrolidin-1-yl-3H-benzimidazol-5-yl)urea
• 化学式: C₂₂H₃₃N₅O
• 分子量: 383.537
• InChiKey: HOPQFLMZUIOTOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  73
• 氢给体数：
  3
• 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 、 tin(II) chloride dihdyrate 、 三乙胺 、 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 32.0h， 生成 5-(4-butylurea)-2-cyclohexyl-6-pyrrolidinyl-1H-benzo[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

• [EN] 5-CARBONYLAMINO-/(SULFONAMIDO-) SUBSTITUTED BENZ IMIDAZOLES AND USE THEREOF TREATMENT OF TUBERCULOSIS<br/>[FR] BENZ IMIDAZOLES SUBSTITUÉS 5-CARBONYLAMINO-/ (SULFONAMIDO-) ET UTILISATION DE CELUI-CI ET LE TRAITEMENT DE LA TUBERCULOSE
  申请人：UNIV NEW YORK STATE RES FOUND

  公开号：WO2013142326A1

  公开（公告）日：2013-09-26

  The present invention discloses novel 5-/6- or 5-/7- substituded benzimidazoles and pharmaceutically acceptable salts thereof. Another aspect of the invention relates to their use in treating a patient infected by Mycobacterium tuberculosis or Francisella tularensis.
• 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.