piperazine-1,4-dicarboxylic acid bis-(4-nitro-phenyl) ester | 6511-92-8

• 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: piperazine-1,4-dicarboxylic acid bis-(4-nitro-phenyl) ester
• 英文别名: bis(4-nitrophenyl) piperazine-1,4-dicarboxylate；1,4-Bis-(4-nitro-phenoxycarbonyl)-piperazin
• CAS: 6511-92-8
• 化学式: C₁₈H₁₆N₄O₈
• 分子量: 416.347
• InChiKey: MMODSVHSSJAXBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.82
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  145.36
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  对硝基苯酚 、 1,4-二(氯羰基)哌嗪 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.5h， 以90%的产率得到piperazine-1,4-dicarboxylic acid bis-(4-nitro-phenyl) ester
  参考文献：
  名称：

  Prodrugs for nitroreductase based cancer therapy-4: Towards prostate cancer targeting: Synthesis of N-heterocyclic nitro prodrugs, Ssap-NtrB enzymatic activation and anticancer evaluation

  摘要：

  In this study, various N-heterocyclic nitro prodrugs (NHN1-16) containing pyrimidine, triazine and piperazine rings were designed and synthesized. The final compounds were identified using FT-IR, ¹H NMR, ¹³C NMR as well as elemental analyses. Enzymatic activities of compounds were conducted by using HPLC analysis to investigate the interaction of substrates with Ssap-NtrB nitroreductase enzyme. MTT assay was performed to evaluate the toxic effect of compounds against Hep3B and PC3 cancer cell lines and healthy HUVEC cell. It was observed that synthesized compounds NHN1-16 exhibited different cytotoxic profiles. Pyrimidine derivative NHN3 and triazine derivative NHN5 can be good drug candidates for prostate cancer with IC₅₀ values of 54.75 µM and 48.9 µM, respectively. Compounds NHN6, NHN10, NHN12, NHN14 and NHN16 were selected as prodrug candidates because of non-toxic properties against three different cell models. The NHN prodrugs and Ssap-NtrB combinations were applied to SRB assay to reveal the prodrug capabilities of these selected compounds. SRB screening results showed that the metabolites of all selected non-toxic compounds showed remarkable cytotoxicity with IC₅₀ values in the range of 1.71-4.72 nM on prostate cancer. Among the tested compounds, especially piperazine derivatives NHN12 and NHN14 showed significant toxic effect with IC₅₀ values of 1.75 nM and 1.79 nM against PC3 cell compared with standart prodrug CB1954 (IC₅₀: 1.71 nM). Novel compounds NHN12 and NHN14 can be considered as promising prodrug candidates for nitroreductase-prodrug based prostate cancer therapy.

  DOI：

  10.1016/j.bioorg.2020.104450