3-amino-5-(4-methylpiperazin-1-yl)-2-nitrobenzoic acid methyl ester | 874301-33-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-amino-5-(4-methylpiperazin-1-yl)-2-nitrobenzoic acid methyl ester
• 英文别名: methyl 3-amino-5-(4-methylpiperazin-1-yl)-2-nitrobenzoate；Methyl 3-amino-5-(4-methyl-1-piperazinyl)-2-nitrobenzoate
• CAS: 874301-33-4
• 化学式: C₁₃H₁₈N₄O₄
• 分子量: 294.31
• InChiKey: RSXLIFYGWZAJSK-UHFFFAOYSA-N

物化性质

• 熔点：
  160-161 °C
• 沸点：
  503.5±50.0 °C(Predicted)
• 密度：
  1.309±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-amino-5-(4-methylpiperazin-1-yl)-2-nitrobenzoic acid methyl ester 在 sodium hydroxide 、 sodium disulfite 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 反应 27.0h， 生成 2'-(4-hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzoimidazoyl-4-carboxylic acid
  参考文献：
  名称：

  Design of New Bidentate Ligands Constructed of Two Hoechst 33258 Units for Discrimination of the Length of Two A₃T₃ Binding Motifs

  摘要：

  The aim of this study is to develop bidentate minor-groove binders that bind the double binding motifs cooperatively. The new bidentate ligands (1) have been designed by connecting two Hoechst 33258 units with a polyether linker for cooperative binding with two remote A(3)T(3) sites of DNA. The linker is introduced to the benzimidazole ring so that it is located at the convex side of the Hoechst unit. DNA binding affinity of the ligands was evaluated by measuring surface plasmon resonance (SPR), circular dichroism, and fluorescence spectra. Interestingly, the bidentate ligands (1) did not show affinity to DNA1 with a single A(3)T(3) motif but showed selective affinity to DNA2 with two A(3)T(3) motifs. The Long Bis-H (1L) having a long polyether linker showed specific binding to DNA2(6) with two A3T3 motifs separated by six nonbinding base pairs. The Long Bis-H (1L) has also shown specific binding to the three-way junction DNA4 with two A(3)T(3) motifs. This study has demonstrated that DNA with double binding motifs can be selectively recognized by the newly designed bidentate ligands.

  DOI：

  10.1021/jo051836t
• 作为产物：
  描述：

  5-氯-2-硝基苯甲酸 在 硫酸 、 potassium tert-butylate 、 甲氧基胺盐酸盐 、 copper diacetate 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.5h， 生成 3-amino-5-(4-methylpiperazin-1-yl)-2-nitrobenzoic acid methyl ester
  参考文献：
  名称：

  Design of New Bidentate Ligands Constructed of Two Hoechst 33258 Units for Discrimination of the Length of Two A₃T₃ Binding Motifs

  摘要：

  The aim of this study is to develop bidentate minor-groove binders that bind the double binding motifs cooperatively. The new bidentate ligands (1) have been designed by connecting two Hoechst 33258 units with a polyether linker for cooperative binding with two remote A(3)T(3) sites of DNA. The linker is introduced to the benzimidazole ring so that it is located at the convex side of the Hoechst unit. DNA binding affinity of the ligands was evaluated by measuring surface plasmon resonance (SPR), circular dichroism, and fluorescence spectra. Interestingly, the bidentate ligands (1) did not show affinity to DNA1 with a single A(3)T(3) motif but showed selective affinity to DNA2 with two A(3)T(3) motifs. The Long Bis-H (1L) having a long polyether linker showed specific binding to DNA2(6) with two A3T3 motifs separated by six nonbinding base pairs. The Long Bis-H (1L) has also shown specific binding to the three-way junction DNA4 with two A(3)T(3) motifs. This study has demonstrated that DNA with double binding motifs can be selectively recognized by the newly designed bidentate ligands.

  DOI：

  10.1021/jo051836t

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，
• Design of New Bidentate Ligands Constructed of Two Hoechst 33258 Units for Discrimination of the Length of Two A₃T₃ Binding Motifs
  作者：Mikimasa Tanada、Saori Tsujita、Shigeki Sasaki

  DOI：10.1021/jo051836t

  日期：2006.1.1

  The aim of this study is to develop bidentate minor-groove binders that bind the double binding motifs cooperatively. The new bidentate ligands (1) have been designed by connecting two Hoechst 33258 units with a polyether linker for cooperative binding with two remote A(3)T(3) sites of DNA. The linker is introduced to the benzimidazole ring so that it is located at the convex side of the Hoechst unit. DNA binding affinity of the ligands was evaluated by measuring surface plasmon resonance (SPR), circular dichroism, and fluorescence spectra. Interestingly, the bidentate ligands (1) did not show affinity to DNA1 with a single A(3)T(3) motif but showed selective affinity to DNA2 with two A(3)T(3) motifs. The Long Bis-H (1L) having a long polyether linker showed specific binding to DNA2(6) with two A3T3 motifs separated by six nonbinding base pairs. The Long Bis-H (1L) has also shown specific binding to the three-way junction DNA4 with two A(3)T(3) motifs. This study has demonstrated that DNA with double binding motifs can be selectively recognized by the newly designed bidentate ligands.