di-tert-butyl 4,4'-(propane-1,3-diyl)bis(piperazine-1-carboxylate) | 1279815-19-8

• 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: di-tert-butyl 4,4'-(propane-1,3-diyl)bis(piperazine-1-carboxylate)
• 英文别名: di-tert-butyl 4,4′-(propane-1,3-diyl)bis(piperazine-1-carboxylate)；tert-butyl 4-[3-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]propyl]piperazine-1-carboxylate
• CAS: 1279815-19-8
• 化学式: C₂₁H₄₀N₄O₄
• 分子量: 412.573
• InChiKey: IJGWQORDEAIERD-UHFFFAOYSA-N

物化性质

• 沸点：
  501.8±50.0 °C(Predicted)
• 密度：
  1.081±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  65.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  di-tert-butyl 4,4'-(propane-1,3-diyl)bis(piperazine-1-carboxylate) 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 1,3-bis(N-(2-(7-chloro-6-oxo-2H-dibenzo[cd,g]indazol-2-yl)ethyl)piperazin-1-yl)propane
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of a novel series of bisintercalating DNA-binding piperazine-linked bisanthrapyrazole compounds as anticancer agents

  摘要：

  A series of bisintercalating DNA binding bisanthrapyrazole compounds containing piperazine linkers were designed by molecular modeling and docking techniques. Because the anthrapyrazoles are not quinones they are unable to be reductively activated like doxorubicin and other anthracyclines and thus they should not be cardiotoxic. The concentration dependent increase in DNA melting temperature was used to determine the strength of DNA binding and the bisintercalation potential of the compounds. Compounds with more than a three-carbon linker that could span four DNA base pairs achieved bisintercalation. All of the bisanthrapyrazoles inhibited human erythroleukemic K562 cell growth in the low to submicromolar concentration range. They also strongly inhibited the decatenation activity of topoisomerase II alpha and the relaxation activity of topoisomerase I. However, as measured by their ability to induce double strand breaks in plasmid DNA, the bisanthrapyrazole compounds did not act as topoisomerase II alpha poisons. In conclusion, a novel group of bisanthrapyrazole compounds were designed, synthesized, and biologically evaluated as potential anticancer agents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.012
• 作为产物：
  描述：

  1,3-二溴丙烷 、 N-Boc-哌嗪 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 生成 di-tert-butyl 4,4'-(propane-1,3-diyl)bis(piperazine-1-carboxylate)
  参考文献：
  名称：

  哌嗪连接的双表鬼臼毒素依托泊苷类似物的基于结构的设计，合成和生物学测试

  摘要：

  靶向DNA拓扑异构酶II的药物，例如表鬼臼毒素依托泊苷，是临床上重要的一类抗癌药。依托泊苷，切割的DNA和拓扑异构酶IIβ的三元复合物的最近公开的X射线结构表明，该复合物中的两个插入的依托泊苷分子被四个DNA碱基对隔开。因此，使用基于结构的设计方法，将一系列具有含哌嗪连接子的双表鬼臼毒素依托泊苷类似物设计为同时结合这两个位点。假设两点结合将产生更稳定的裂解复合物和更有效的抗癌药。最有效的双-表鬼臼毒素对人红白血病K562细胞的生长抑制作用比依托泊苷高10倍，它含有一个带有8个亚甲基的连接基。在各种测定中，所有的单-和双-表鬼臼毒素都显示出有力的证据表明它们靶向拓扑异构酶II。NCI 60细胞GI的比较分析50个终点数据也与这些靶向拓扑异构酶II的化合物一致。

  DOI：

  10.1016/j.bmc.2015.04.022

文献信息

• BIS-DIAZENIUMDIOLATE COMPOUNDS AS ANTI-CANCER AGENTS
  申请人：Arizona board of regents on behalf of Arizona State University

  公开号：US20190106396A1

  公开（公告）日：2019-04-11

  A series of double-component, bis O 2 -aryl diazeniumdiolate derivatives are provided, of which each molecule can release up to four nitric oxide molecules. These compounds show cytotoxic activities to cancer cells, such as human leukemia, breast cancer and lung cancer. Among them, the compound 3 showed the highest specific activity against human leukemia cells.

  提供了一系列双组分的双O2-芳基重氮二氧酸盐衍生物，每个分子可以释放高达四个一氧化氮分子。这些化合物对癌细胞具有细胞毒性活性，如人类白血病、乳腺癌和肺癌。其中，化合物3对人类白血病细胞表现出最高的特异性活性。
• Bis-diazeniumdiolate compounds as anti-cancer agents
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US10556875B2

  公开（公告）日：2020-02-11

  A series of double-component, bis O2-aryl diazeniumdiolate derivatives are provided, of which each molecule can release up to four nitric oxide molecules. These compounds show cytotoxic activities to cancer cells, such as human leukemia, breast cancer and lung cancer. Among them, the compound 3 showed the highest specific activity against human leukemia cells.

  本研究提供了一系列双组分、双 O2- 芳基二氮杂环戊烷衍生物，其中每个分子可释放多达四个一氧化氮分子。这些化合物对人类白血病、乳腺癌和肺癌等癌细胞具有细胞毒活性。其中，化合物 3 对人类白血病细胞的特异性活性最高。
• Double-component diazeniumdiolate derivatives as anti-cancer agents
  作者：Xun Ji、Qi Chen、Viswanath Arutla、Omar Khdour、Qiong-Ying Hu、Shengxi Chen

  DOI：10.1016/j.bmc.2020.115405

  日期：2020.4

  In this study, we synthesized a series of double-component O-2-aryl diazeniumdiolate (DDNO) derivatives, of which each molecule can release up to four nitric oxide molecules. These compounds showed cytotoxic activities to cancer cells, such as human leukemia, breast cancer and lung cancer. Among them, compound 1 (DDNO-1) showed the highest specific activity to human leukemia cells. It induced cell apopotosis and arrest cell cycle of G(2)/M phase. The JNK and p38 protein kinases were activated by compound 1 to induce cancer cell apoptosis. Compound 1 also increased pro-apoptotic Bax level, which is a same function compared to a reported NO donor, JS-K. More interestingly, it decreased the level of an anti-apoptotic member Bcl-2, which is an opposite effect compared to JS-K. Compound 1 could be developed as a new anti-cancer agent since it increases the Bax/Bcl-2 ratio to overcome the drug resistance.