3-(N',N',N-trimethylethylenediamino)-4,6-dinitroaniline | 1259926-73-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(N',N',N-trimethylethylenediamino)-4,6-dinitroaniline
• CAS: 1259926-73-2
• 化学式: C₁₁H₁₇N₅O₄
• 分子量: 283.287
• InChiKey: PEVDKVLVYNTRKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.08
• 重原子数：
  20.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  118.78
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-(N',N',N-trimethylethylenediamino)-4,6-dinitroaniline 在 吡啶 、 盐酸 、 tin(II) chloride dihdyrate 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 5-benzenesulfonamido-2-cyclohexyl-6-(N',N',N-trimethyl-ethylenediamino)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Benzimidazole-based antibacterial agents against Francisella tularensis

  摘要：

  Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 mu g/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35-48.6 mu g/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 mu g/mL. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.059
• 作为产物：
  描述：

  2,4-二硝基-5-氟苯胺 、 N,N,N'-三甲基乙二胺 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以93%的产率得到3-(N',N',N-trimethylethylenediamino)-4,6-dinitroaniline
  参考文献：
  名称：

  新型三取代苯并咪唑，靶向 Mtb FtsZ，作为新型抗结核药物

  摘要：

  通过合理的药物设计创建了新型三取代苯并咪唑文库。大量这些苯并咪唑表现出有希望的 MIC 值在 0.5-6 μg/mL (2-15 μM) 范围内，因为它们对Mtb H37Rv 菌株具有抗菌活性。此外，五种先导化合物还对具有不同耐药性的临床Mtb菌株表现出优异的活性。所有先导化合物对 Vero 细胞均未表现出明显的细胞毒性（IC 50 > 200 μM），其以剂量依赖性方式抑制Mtb FtsZ 组装。这两种先导化合物出人意料地显示出Mtb的 GTPase 活性增强FtsZ。结果强烈表明，增加的 GTPase 活性使 FtsZ 组装不稳定，从而有效抑制 FtsZ 聚合和细丝形成。分别用先导化合物处理的Mtb FtsZ 和Mtb细胞的 TEM 和 SEM 分析强烈表明，苯并咪唑铅对抑制Mtb FtsZ 组装和 Z 环形成具有新的作用机制。

  DOI：

  10.1021/jm1012006

文献信息

• 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.