1,4-bis[6-(3,4,5,6-tetrahydropyrimidin-2-yl)indol-2-yl]benzene | 1225332-95-5

• 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
• 英文别名: MBX-1162；2,2'-Benzene-1,4-Diylbis[6-(1,4,5,6-Tetrahydropyrimidin-2-Yl)-1h-Indole]；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
• CAS: 1225332-95-5
• 化学式: C₃₀H₂₈N₆
• 分子量: 472.593
• InChiKey: CYZKZDNPVSMEPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  80.4
• 氢给体数：
  4
• 氢受体数：
  2

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 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 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：

  4,4-(1E,1E)-2,2-(1,4-phenylene)-bis(ethene-2,1-diyl)bis(3-nitrobenzonitrile) 在 磷酸三乙酯 作用下， 反应 96.0h， 生成 1,4-bis[6-(3,4,5,6-tetrahydropyrimidin-2-yl)indol-2-yl]benzene
  参考文献：
  名称：

  Antibacterial Drug Leads: DNA and Enzyme Multitargeting

  摘要：

  We report the results of an investigation of the activity of a series of amidine and bisamidine compounds against Staphylococcus aureus and Escherichia coli. The most active compounds bound to an AT-rich DNA dodecamer (CGCGAATTCGCG)(2) and using DSC were found to increase the melting transition by up to 24 degrees C. Several compounds also inhibited undecaprenyl diphosphate synthase (UPPS) with IC50 values of 100-500 nM, and we found good correlations (R-2 = 0.89, S. aureus; R-2 = 0.79, E. coli) between experimental and predicted cell growth inhibition by using DNA Delta(Tm) and UPPS IC50 experimental results together with one computed descriptor. We also solved the structures of three bisamidines binding to DNA as well as three UPPS structures. Overall, the results are of general interest in the context of the development of resistance-resistant antibiotics that involve multitargeting.

  DOI：

  10.1021/jm501449u

文献信息

• [EN] ANTIFUNGAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIFONGIQUES
  申请人：MICROBIOTIX INC

  公开号：WO2013052263A2

  公开（公告）日：2013-04-11

  The invention provides fungicide and/or antifungal organic compounds and compositions thereof that kill or inhibit growth of cells of one or more microbial pathogens.
• Antibacterial Drug Leads: DNA and Enzyme Multitargeting
  作者：Wei Zhu、Yang Wang、Kai Li、Jian Gao、Chun-Hsiang Huang、Chun-Chi Chen、Tzu-Ping Ko、Yonghui Zhang、Rey-Ting Guo、Eric Oldfield

  DOI：10.1021/jm501449u

  日期：2015.2.12

  We report the results of an investigation of the activity of a series of amidine and bisamidine compounds against Staphylococcus aureus and Escherichia coli. The most active compounds bound to an AT-rich DNA dodecamer (CGCGAATTCGCG)(2) and using DSC were found to increase the melting transition by up to 24 degrees C. Several compounds also inhibited undecaprenyl diphosphate synthase (UPPS) with IC50 values of 100-500 nM, and we found good correlations (R-2 = 0.89, S. aureus; R-2 = 0.79, E. coli) between experimental and predicted cell growth inhibition by using DNA Delta(Tm) and UPPS IC50 experimental results together with one computed descriptor. We also solved the structures of three bisamidines binding to DNA as well as three UPPS structures. Overall, the results are of general interest in the context of the development of resistance-resistant antibiotics that involve multitargeting.
• Potent and broad-spectrum antibacterial activity of indole-based bisamidine antibiotics: Synthesis and SAR of novel analogs of MBX 1066 and MBX 1090
  作者：John D. Williams、Son T. Nguyen、Shen Gu、Xiaoyuan Ding、Michelle M. Butler、Tommy F. Tashjian、Timothy J. Opperman、Rekha G. Panchal、Sina Bavari、Norton P. Peet、Donald T. Moir、Terry L. Bowlin

  DOI：10.1016/j.bmc.2013.10.014

  日期：2013.12

  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.