1,4-bis[6-(3,4,5,6-tetrahydropyrimidin-2-yl)indol-2-yl]benzene trifluoroacetic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1,4-bis[6-(3,4,5,6-tetrahydropyrimidin-2-yl)indol-2-yl]benzene trifluoroacetic acid
• 英文别名: 6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-[4-[6-(1,4,5,6-tetrahydropyrimidin-2-yl)-1H-indol-2-yl]phenyl]-1H-indole;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₃₀H₂₈N₆
• 分子量: 586.616
• InChiKey: ZAVJRZUEAMJGSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  43
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,4-bis[6-(3,4,5,6-tetrahydropyrimidin-2-yl)indol-2-yl]benzene trifluoroacetic acid 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以85 mg的产率得到2,5-bis[3-bromo-6-(3,4,5,6-tetrahydropyrimidin-2-yl)indol-2-yl]benzene trifluoroacetic acid
  参考文献：
  名称：

  Potent and broad-spectrum antibacterial activity of indole-based bisamidine antibiotics: Synthesis and SAR of novel analogs of MBX 1066 and MBX 1090

  摘要：

  The prevalence of drug-resistant bacteria in the clinic has propelled a concerted effort to find new classes of antibiotics that will circumvent current modes of resistance. We have previously described a set of bisamidine antibiotics that contains a core composed of two indoles and a central linker. The first compounds of the series, MBX 1066 and MBX 1090, have potent antibacterial properties against a wide range of Gram-positive and Gram-negative bacteria. We have conducted a systematic exploration of the amidine functionalities, the central linker, and substituents at the indole 3-position to determine the factors involved in potent antibacterial activity. Some of the newly synthesized compounds have even more potent and broad-spectrum activity than MBX 1066 and MBX 1090. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.10.014
• 作为产物：
  描述：

  4-甲基-3-硝基苯甲腈 在 哌啶 、 环丁砜 、 tetraphosphorus decasulfide 作用下， 反应 50.75h， 生成 1,4-bis[6-(3,4,5,6-tetrahydropyrimidin-2-yl)indol-2-yl]benzene trifluoroacetic acid
  参考文献：
  名称：

  Synthesis and structure-activity relationship of novel bisindole amidines active against MDR Gram-positive and Gram-negative bacteria

  摘要：

  A series of novel diamidines with N-substituents on an amidine N-atom were synthesized and evaluated for their cytotoxicity and in vitro antibacterial activity against a range of Gram-positive and Gram-negative bacterial strains. Based on structure-activity relationship, N-substituents with a branched chain and a shorter carbon chain on the amidine N-atom exhibited more promising activity against Gram-negative and MDR-Gram-positive bacteria: compounds 5c and Si were the most powerful candidate compounds. Compound 5c showed greater efficacy than levofloxacin against most drug resistant Gram-positive bacteria and exhibited broad-spectrum antibacterial activity against Gram-negative bacteria, with MIC values in the range of 2-16 mu g/mL. Slightly more potent antibacterial activity against Klebsiella pneumoniae, Acinetobacter calcoaceticus, Enterobacter cloacae, and Proteus mirabilis was observed for 5i in comparison with 5c. Compound 5i also showed remarkable antibacterial activity against NDM-1-producing Gram-negative bacteria, with MIC values in the range of 2-4 mu g/mL, and was superior to the reference drugs meropenem and levofloxacin. Effective antibacterial activity of 5i was also shown in vivo in a mouse model of Staphylococcus aureus MRSA strain, with an ED(50)values of 2.62 mg/kg. (C) 2018 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2018.03.031