6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole | 1268487-44-0

• 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: 6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole
• 英文别名: DPA 112；6-(4-methylpiperazin-1-yl)-2-[4-[2-(4-oct-7-ynyltriazol-1-yl)ethoxy]phenyl]-1H-benzimidazole
• CAS: 1268487-44-0
• 化学式: C₃₀H₃₇N₇O
• 分子量: 511.67
• InChiKey: RJBXTFOTVBNFBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  75.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5″-azide-1,3,2′,6′,2′″,6′″-hexa-N-(tert-butoxycarbonyl)-5″-deoxy-neomycin B 、 6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 乙醇 为溶剂， 生成
  参考文献：
  名称：

  Recognition of HIV-TAR RNA using neomycin–benzimidazole conjugates

  摘要：

  Synthesis of a novel class of compounds and their biophysical studies with TAR-RNA are presented. The synthesis of these compounds was achieved by conjugating neomycin, an aminoglycoside, with benzimidazoles modeled from a B-DNA minor groove binder, Hoechst 33258. The neomycin-benzimidazole conjugates have varying linkers that connect the benzimidazole and neomycin units. The linkers of varying length (5-23 atoms) in these conjugates contain one to three triazole units. The UV thermal denaturation experiments showed that the conjugates resulted in greater stabilization of the TAR-RNA than either neomycin or benzimidazole used in the synthesis of conjugates. These results were corroborated by the FID displacement and tat-TAR inhibition assays. The binding of ligands to the TAR-RNA is affected by the length and composition of the linker. Our results show that increasing the number of triazole groups and the linker length in these compounds have diminishing effect on the binding to TAR-RNA. Compounds that have shorter linker length and fewer triazole units in the linker displayed increased affinity towards the TAR RNA. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.014
• 作为产物：
  描述：

  4-(4-甲基哌嗪基)-1,2-苯二胺 在 sodium metabisulfite 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Hoechst 33258衍生的单和双苯并咪唑对大肠杆菌RNA和DNA拓扑异构酶I的选择性抑制

  摘要：

  已经合成了一系列基于Hoechst 33258的单和双苯并咪唑类化合物，并评估了它们对大肠杆菌DNA拓扑异构酶I的抑制作用，与​​B-DNA双链体的结合以及抗菌活性。具有炔基侧链的双苯并咪唑类化合物具有出色的大肠杆菌DNA拓扑异构酶I抑制特性，IC 50值<5.0μM。几个bisbenzimidazoles（3，6，7，8）也抑制拓扑异构酶的RNA的活性的大肠杆菌DNA拓扑异构酶I.对于革兰氏阳性菌株，双苯并咪唑类抑制细菌生长的效果比单苯并咪唑类更好。革兰氏阳性菌（肠球菌和葡萄球菌，包括两个MRSA菌株0.3–8μg/ mL）的最低抑菌浓度（MIC）比大多数革兰氏阴性菌（铜绿假单胞菌，16–32μg）低/ mL，肺炎克雷伯菌> 32μg/ mL）。Bisbenzimidazoles具有稳定的B-DNA双链体（1.2−23.4°C），细胞毒性研究表明，类似的变化取决于侧链长度。建模研究表明，

  DOI：

  10.1021/acs.jmedchem.7b00191

文献信息

• Selective Inhibition of<i>Escherichia coli</i>RNA and DNA Topoisomerase I by Hoechst 33258 Derived Mono- and Bisbenzimidazoles
  作者：Nihar Ranjan、Sandra Story、Geraldine Fulcrand、Fenfei Leng、Muzammil Ahmad、Ada King、Souvik Sur、Weidong Wang、Yuk-Ching Tse-Dinh、Dev P. Arya

  DOI：10.1021/acs.jmedchem.7b00191

  日期：2017.6.22

  Escherichia coli DNA topoisomerase I inhibition, binding to B-DNA duplex, and antibacterial activity has been evaluated. Bisbenzimidazoles with alkynyl side chains display excellent E. coli DNA topoisomerase I inhibition properties with IC50 values <5.0 μM. Several bisbenzimidazoles (3, 6, 7, 8) also inhibit RNA topoisomerase activity of E. coli DNA topoisomerase I. Bisbenzimidazoles inhibit bacterial growth

  已经合成了一系列基于Hoechst 33258的单和双苯并咪唑类化合物，并评估了它们对大肠杆菌DNA拓扑异构酶I的抑制作用，与​​B-DNA双链体的结合以及抗菌活性。具有炔基侧链的双苯并咪唑类化合物具有出色的大肠杆菌DNA拓扑异构酶I抑制特性，IC 50值<5.0μM。几个bisbenzimidazoles（3，6，7，8）也抑制拓扑异构酶的RNA的活性的大肠杆菌DNA拓扑异构酶I.对于革兰氏阳性菌株，双苯并咪唑类抑制细菌生长的效果比单苯并咪唑类更好。革兰氏阳性菌（肠球菌和葡萄球菌，包括两个MRSA菌株0.3–8μg/ mL）的最低抑菌浓度（MIC）比大多数革兰氏阴性菌（铜绿假单胞菌，16–32μg）低/ mL，肺炎克雷伯菌> 32μg/ mL）。Bisbenzimidazoles具有稳定的B-DNA双链体（1.2−23.4°C），细胞毒性研究表明，类似的变化取决于侧链长度。建模研究表明，
• Recognition of HIV-TAR RNA using neomycin–benzimidazole conjugates
  作者：Nihar Ranjan、Sunil Kumar、Derrick Watkins、Deyun Wang、Daniel H. Appella、Dev P. Arya

  DOI：10.1016/j.bmcl.2013.08.014

  日期：2013.10

  Synthesis of a novel class of compounds and their biophysical studies with TAR-RNA are presented. The synthesis of these compounds was achieved by conjugating neomycin, an aminoglycoside, with benzimidazoles modeled from a B-DNA minor groove binder, Hoechst 33258. The neomycin-benzimidazole conjugates have varying linkers that connect the benzimidazole and neomycin units. The linkers of varying length (5-23 atoms) in these conjugates contain one to three triazole units. The UV thermal denaturation experiments showed that the conjugates resulted in greater stabilization of the TAR-RNA than either neomycin or benzimidazole used in the synthesis of conjugates. These results were corroborated by the FID displacement and tat-TAR inhibition assays. The binding of ligands to the TAR-RNA is affected by the length and composition of the linker. Our results show that increasing the number of triazole groups and the linker length in these compounds have diminishing effect on the binding to TAR-RNA. Compounds that have shorter linker length and fewer triazole units in the linker displayed increased affinity towards the TAR RNA. (C) 2013 Elsevier Ltd. All rights reserved.