2-(4-(3,4-diamino phenyl)piperazin-1-yl)ethanol | 485841-41-6

• 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: 2-(4-(3,4-diamino phenyl)piperazin-1-yl)ethanol
• 英文别名: 2-[4-(3,4-Diaminophenyl)piperazin-1-yl]ethanol
• CAS: 485841-41-6
• 化学式: C₁₂H₂₀N₄O
• 分子量: 236.317
• InChiKey: KFXWPDVLLXNAMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  78.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-(3,4-diamino phenyl)piperazin-1-yl)ethanol 、 6H,12H-5,11-methanodibenzo[b,f] [1,5]diazocine-2,8-dicarbaldehyde 在 sodium metabisulfite 作用下， 以 水 为溶剂， 反应 12.0h， 以63%的产率得到2-[4-[2-[13-[6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1,9-diazatetracyclo[7.7.1.02,7.010,15]heptadeca-2(7),3,5,10(15),11,13-hexaen-5-yl]-3H-benzimidazol-5-yl]piperazin-1-yl]ethanol
  参考文献：
  名称：

  Stabilization and Structural Alteration of the G-Quadruplex DNA Made from the Human Telomeric Repeat Mediated by Tröger’s Base Based Novel Benzimidazole Derivatives

  摘要：

  Ligand-induced stabilization of the G-quadruplex DNA structure derived from the single-stranded 3'-overhang of the telomeric DNA is an attractive strategy for the inhibition of the telomerase activity. The agents that can induce/stabilize a DNA sequence into a G-quadruplex structure are therefore potential anticancer drugs. Herein we present the first report of the interactions of two novel bisbenzimidazoles (TBBz1 and TBBz2) based on Troger's base skeleton with the G-quadruplex DNA (G4DNA). These Troger's base molecules stabilize the G4DNA derived from a human telomeric sequence. Evidence of their strong interaction with the G4DNA has been obtained from CD spectroscopy, thermal denaturation, and UV-vis titration studies. These ligands also possess significantly higher affinity toward the G4DNA over the duplex DNA. The above results obtained are in excellent agreement with the biological activity, measured in vitro using a modified TRAP assay. Furthermore, the ligands are selectively more cytotoxic toward the cancerous cells than the corresponding noncancerous cells. Computational studies suggested that the adaptive scaffold might allow these ligands to occupy not only the G-quartet planes but also the grooves of the G4DNA.

  DOI：

  10.1021/jm300442r
• 作为产物：
  描述：

  2-(4-(3-amino-4-nitrophenyl)piperazin-1-yl)ethan-1-ol 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以100%的产率得到2-(4-(3,4-diamino phenyl)piperazin-1-yl)ethanol
  参考文献：
  名称：

  New dimeric carbazole–benzimidazole mixed ligands for the stabilization of human telomeric G-quadruplex DNA and as telomerase inhibitors. A remarkable influence of the spacer

  摘要：

  G-四链体DNA结合二聚配体及其端粒酶抑制活性已被报道。

  DOI：

  10.1039/c5ob00675a

文献信息

• New dimeric carbazole–benzimidazole mixed ligands for the stabilization of human telomeric G-quadruplex DNA and as telomerase inhibitors. A remarkable influence of the spacer
  作者：Basudeb Maji、Krishan Kumar、K. Muniyappa、Santanu Bhattacharya

  DOI：10.1039/c5ob00675a

  日期：——

  G-quadruplex DNA binding dimeric ligands and their telomerase inhibition activity are reported.

  G-四链体DNA结合二聚配体及其端粒酶抑制活性已被报道。
• <i>N</i>-Aryl-2-aminobenzimidazoles: Novel, Efficacious, Antimalarial Lead Compounds
  作者：Sreekanth Ramachandran、Shahul Hameed P.、Abhishek Srivastava、Gajanan Shanbhag、Sapna Morayya、Nikhil Rautela、Disha Awasthy、Stefan Kavanagh、Sowmya Bharath、Jitendar Reddy、Vijender Panduga、K. R. Prabhakar、Ramanatha Saralaya、Robert Nanduri、Anandkumar Raichurkar、Sreenivasaiah Menasinakai、Vijayashree Achar、María Belén Jiménez-Díaz、María Santos Martínez、Iñigo Angulo-Barturen、Santiago Ferrer、Laura María Sanz、Francisco Javier Gamo、Sandra Duffy、Vicky M. Avery、David Waterson、Marcus C. S. Lee、Olivia Coburn-Flynn、David A. Fidock、Pravin S. Iyer、Shridhar Narayanan、Vinayak Hosagrahara、Vasan K. Sambandamurthy

  DOI：10.1021/jm500715u

  日期：2014.8.14

  malaria. This compound displayed an excellent pharmacokinetic profile with a long half-life (19 h) in rat blood. This profile led to an extended survival of animals for over 30 days following a dose of 50 mg/kg in the Pb malaria model. Compound 12 retains its potency against a panel of Pf isolates with known mechanisms of resistance. The fast killing observed in the in vitro parasite reduction ratio (PRR)

  从阿斯利康公司化合物集合的表型筛选中，N-芳基-2-氨基苯并咪唑类化合物已成为对抗恶性疟原虫（Pf）无性血液阶段的新命中。药物化学对Pf和ADME性质的效力进行了优化，从而确定了12种为先导分子。化合物12在疟疾的伯氏疟原虫（Pb）模型中有效。该化合物在大鼠血液中显示出出色的药代动力学特征，具有长的半衰期（19小时）。在Pb剂量为50 mg / kg时，此特征导致动物延长了30天以上的生存期疟疾模型。化合物12保持其对具有已知抗性机制的Pf分离物组的效力。在体外寄生虫减少率（PRR）分析中观察到的快速杀灭作用与延长的生存期一起突显了这种新颖的化学类别用于治疗疟疾的希望。
• Indazole benzimidazole compounds
  申请人：Chiron Corporation

  公开号：US20030207883A1

  公开（公告）日：2003-11-06

  Organic compounds having the structure I are provided where the variables have the values described herein. 1 Pharmaceutical formulations and medicaments include the organic compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier and may be prepared by mixing the organic compound or a pharmaceutically acceptable salt of the organic compound with a carrier and water. A method of treating a patient includes administering a pharmaceutical formulation or medicament according to the invention to a patient in need thereof.

  提供具有结构I的有机化合物，其中变量具有所述的值。1药物制剂和药物包括该有机化合物或其药学上可接受的盐和药学上可接受的载体，并可通过将该有机化合物或其药学上可接受的盐与载体和水混合制备。治疗患者的方法包括向需要该药物的患者施用本发明的药物制剂或药物。
• Dimeric 1,3-Phenylene-bis(piperazinyl benzimidazole)s: Synthesis and Structure–Activity Investigations on their Binding with Human Telomeric G-Quadruplex DNA and Telomerase Inhibition Properties
  作者：Akash K Jain、Ananya Paul、Basudeb Maji、K. Muniyappa、Santanu Bhattacharya

  DOI：10.1021/jm200860b

  日期：2012.4.12

  Ligand-induced stabilization of G-quadruplex structures formed by the human telomeric DNA is an active area of research. The compounds which stabilize the G-quadruplexes often lead to telomerase inhibition. Herein we present the results of interaction of new monomeric and dimeric ligands having 1,3-phenylene-bis(piperazinyl benzimidazole) unit with G-quadruplex DNA (G4DNA) formed by human telomeric repeat d[(G(3)T(2)A)(3)G(3)]. These ligands efficiently stabilize the preformed G4DNA in the presence of 100 mM monovalent alkali metal ions. Also, the G4DNA formed in the presence of low concentrations of ligands in 100 mM K+ adopts a highly stable parallel-stranded conformation. The G-quadruplexes formed in the presence of the dimeric compound are more stable than that induced by the corresponding monomeric counterpart. The dimeric ligands having oligo-oxyethylene spacers provide much higher stability to the preformed G4DNA and also exert significantly higher telomerase inhibition activity. Computational aspects have also been discussed.
• Design and Synthesis of New Benzimidazole–Carbazole Conjugates for the Stabilization of Human Telomeric DNA, Telomerase Inhibition, and Their Selective Action on Cancer Cells
  作者：Basudeb Maji、Krishan Kumar、Mangesh Kaulage、K. Muniyappa、Santanu Bhattacharya

  DOI：10.1021/jm500427n

  日期：2014.8.28

  Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole-carbazole conjugates and demonstrate their high binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.