4-(4-methoxyphenyl)piperazine-1-carbothiohydrazide | 1355695-97-4

• 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: 4-(4-methoxyphenyl)piperazine-1-carbothiohydrazide
• 英文别名: 4-(4-Methoxyphenyl)piperazine-1-carbothiohydrazide
• CAS: 1355695-97-4
• 化学式: C₁₂H₁₈N₄OS
• 分子量: 266.367
• InChiKey: IKUQKJRQBZRPMT-UHFFFAOYSA-N

物化性质

• 沸点：
  446.6±55.0 °C(Predicted)
• 密度：
  1.257±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  85.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-喹喔啉甲醛 、 4-(4-methoxyphenyl)piperazine-1-carbothiohydrazide 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 0.33h， 以86%的产率得到4-(4-methoxyphenyl)-N'-[(quinoxalin-2-yl)methylidene]piperazine-1-carbothiohydrazide
  参考文献：
  名称：

  Anticancer activity of the thiosemicarbazones that are based on di-2-pyridine ketone and quinoline moiety

  摘要：

  Thiosemicarbazones (TSC) are a subclass of iron-chelating agents that are believed to have an anticancer activity. The high potential for the application of this compound class can be illustrated by a fact that three TSC have entered clinical trials. The ability to chelate metal ions results in several biochemical changes in the cellular metabolism and growth. An important factor that determines the antitumor activity of TSC is a level of iron regulatory proteins and the antioxidant potential that is specific for each type of cancer cell. However, despite the increasing interest in TSC, their mechanism of anticancer activity is still unclear. For a more effective and rational design, it is crucial to determine and describe the abovementioned issues. In this report, we describe a series of new TSC that are designed on the four main structural scaffolds. The anticancer activity of these compounds was evaluated against a panel of cancer cell lines including colon and breast cancers and gliomas. Special attention was paid to the metal dependent proteins. The impact of the tested TSC on the cell cycle and redox homeostasis was also determined. These results confirm a p53-independent mechanism of apoptosis. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.027
• 作为产物：
  描述：

  1-(4-甲氧基苯基)哌嗪 在 hydrazine hydrate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 4-(4-methoxyphenyl)piperazine-1-carbothiohydrazide
  参考文献：
  名称：

  Piperazinyl fragment improves anticancer activity of Triapine

  摘要：

  设计了一类包含哌嗪的Triapine（哌嗪类似物）作为靶向铁硫簇（TSCs）的新一类化合物，旨在实现TSCs的N4位置上的二取代模式，这是先前获得的具有高活性的TSC化合物–DpC和Dp44mT的关键前提。我们测试了新型化合物L1-L12的重要物理化学特性。这些配体在生理pH下呈中性，这使得它们比亲脂性较低的配体（如DFO）更容易穿透细胞膜并结合细胞内的铁库。在多种癌细胞类型中检测了这些新型TSCs的选择性和抗癌活性。总体而言，这些新型化合物展现出最有希望作为抗癌剂，具有强效且选择性的抗增殖活性。我们更深入地研究了这些化合物的作用机制，发现它们能够抑制细胞周期（G1/S期）。此外，我们还检测到了依赖于细胞系特定遗传背景的凋亡现象。因此，构效关系研究表明，哌嗪环与Triapine的结合使得能够识别出具有强效且选择性的抗癌螯合剂，这些螯合剂值得进一步进行体内研究。值得注意的是，这项研究证明了胺N4功能的二取代模式的重要性。

  DOI：

  10.1371/journal.pone.0188767

文献信息

• Piperazinyl fragment improves anticancer activity of Triapine
  作者：Marta Rejmund、Anna Mrozek-Wilczkiewicz、Katarzyna Malarz、Monika Pyrkosz-Bulska、Kamila Gajcy、Mieczyslaw Sajewicz、Robert Musiol、Jaroslaw Polanski

  DOI：10.1371/journal.pone.0188767

  日期：——

  A new class of TSCs containing piperazine (piperazinylogs) of Triapine, was designed to fulfill the di-substitution pattern at the TSCs N4 position, which is a crucial prerequisite for the high activity of the previously obtained TSC compounds–DpC and Dp44mT. We tested the important physicochemical characteristics of the novel compounds L1-L12. The studied ligands are neutral at physiological pH, which allows them to permeate cell membranes and bind cellular Fe pools more readily than less lipid-soluble ligands, e.g. DFO. The selectivity and anti-cancer activity of the novel TSCs were examined in a variety of cancer cell types. In general, the novel compounds demonstrated the greatest promise as anti-cancer agents with both a potent and selective anti-proliferative activity. We investigated the mechanism of action more deeply, and revealed that studied compounds inhibit the cell cycle (G1/S phase). Additionally we detected apoptosis, which is dependent on cell line’s specific genetic profile. Accordingly, structure-activity relationship studies suggest that the combination of the piperazine ring with Triapine allows potent and selective anticancer chelators that warrant further in vivo examination to be identified. Significantly, this study proved the importance of the di-substitution pattern of the amine N4 function.

  设计了一类包含哌嗪的Triapine（哌嗪类似物）作为靶向铁硫簇（TSCs）的新一类化合物，旨在实现TSCs的N4位置上的二取代模式，这是先前获得的具有高活性的TSC化合物–DpC和Dp44mT的关键前提。我们测试了新型化合物L1-L12的重要物理化学特性。这些配体在生理pH下呈中性，这使得它们比亲脂性较低的配体（如DFO）更容易穿透细胞膜并结合细胞内的铁库。在多种癌细胞类型中检测了这些新型TSCs的选择性和抗癌活性。总体而言，这些新型化合物展现出最有希望作为抗癌剂，具有强效且选择性的抗增殖活性。我们更深入地研究了这些化合物的作用机制，发现它们能够抑制细胞周期（G1/S期）。此外，我们还检测到了依赖于细胞系特定遗传背景的凋亡现象。因此，构效关系研究表明，哌嗪环与Triapine的结合使得能够识别出具有强效且选择性的抗癌螯合剂，这些螯合剂值得进一步进行体内研究。值得注意的是，这项研究证明了胺N4功能的二取代模式的重要性。
• Synthesis, antimicrobial studies, and molecular docking of some new dihydro-1,3,4-thiadiazole and pyrazole derivatives derived from dithiocarbazates
  作者：Amr Hassan Moustafa、Doaa H. Ahmed、Mohamed T. M. El-Wassimy、Mamdouh F. A. Mohamed

  DOI：10.1080/00397911.2020.1843179

  日期：2021.2.16

  A series of 3-acetyl-2-aryl-5-methylthio-2,3-dihydro-1,3,4-thiadiazoles 3a–g, N- (4-acetyl-5-aryl-4,5-dihydro-1,3,4-thiadiazol-2-yl) acetamide derivatives 5a–e and spiro-compound 7 was prepared fro...

  一系列 3-乙酰-2-芳基-5-甲硫基-2,3-二氢-1,3,4-噻二唑 3a–g, N-(4-乙酰-5-芳基-4,5-二氢-1 ,3,4-噻二唑-2-基)乙酰胺衍生物 5a-e 和螺环化合物 7 是由...
• The synthesis and tuberculostatic activity of benzenesulfonohydrazide derivatives
  作者：Krystyna Wisterowicz、Katarzyna Gobis、Henryk Foks、Ewa Augustynowicz-Kopeć

  DOI：10.1002/hc.20743

  日期：——

  chlorides with various aminocarbothiohydrazides. The structures were confirmed by IR and NMR spectra as well as elemental analysis. All of the obtained compounds were screened in vitro for their tuberculostatic activity. Preliminary results indicated that some target compounds exhibited promising results, especially toward Mycobacterium tuberculosis (Mtb) resistant strain 210. © 2011 Wiley Periodicals

  通过苯磺酰氯与各种氨基碳硫酰肼反应合成了一系列新型N'-氨基碳硫酰-苯磺酰肼。结构经红外光谱和核磁共振光谱以及元素分析证实。对所有获得的化合物进行体外抗结核活性筛选。初步结果表明，一些目标化合物表现出有希望的结果，尤其是对结核分枝杆菌 (Mtb) 耐药菌株 210。 © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:99–104, 2012；在 wileyonlinelibrary.com 上在线查看这篇文章。DOI 10.1002/hc.20743
• Impact of thiosemicarbazones on the accumulation of PpIX and the expression of the associated genes
  作者：Robert Gawecki、Katarzyna Malarz、Marta Rejmund、Jaroslaw Polanski、Anna Mrozek-Wilczkiewicz

  DOI：10.1016/j.jphotobiol.2019.111585

  日期：2019.10

  Thiosemicarbazone derivatives are known for their broad biological activity including their antitumor potency. The aim of the current study was to examine the effect of a novel series of non-toxic iron chelators on the accumulation of protoporphyrin IX after external 5-aminolevulonic acid administration. From this series we selected one the most promising derivative which causes a pronounced increase in the concentration of protoporphyrin IX. The increase of the photosensitizer concentration is necessary for the trigger the efficient therapeutic effect of the photodynamic reaction. For selected compound 2 we performed an examination of a panel of the genes that are involved in the heme biosynthesis and degradation. Results indicated the crucial roles of ferrochelatase and heme oxygenase in the described processes. Surprisingly, there was a strict dependence on the type of the tested cell line. A decrease in the expression of the two aforementioned enzymes after incubation with compound 2 and 5-aminolevulonic acid is a commonly known fact and we detected this trend for the MCF-7 and HCT 116 cell lines. However, we noticed the upregulation of the tested targets for the Hs683 cells. These unconventional results prompted us to do a more in-depth analysis of the described processes. In conclusion, we found that compound 2 is a novel, highly effective booster of photodynamic therapy that has prospective applications.
• Synthesis and antiproliferative evaluation of piperazine-1-carbothiohydrazide derivatives of indolin-2-one
  作者：Hui-Hui Lin、Wei-Yao Wu、Sheng-Li Cao、Ji Liao、Li Ma、Man Gao、Zhong-Feng Li、Xingzhi Xu

  DOI：10.1016/j.bmcl.2013.03.099

  日期：2013.6

  By varying the substituents (R-1) at the indolin-2-one scaffold, a series of indolin-2-one derivatives bearing 4-phenylpiperazine-1-carbothiohydrazide moiety at the C3-position were synthesized and evaluated for their antiproliferative activity against three human cancer cell lines. We further selected the 5-chloroindolin-2-one moiety for the extension to another series of compounds by varying the substituents (R-2) at the phenyl group connected with the piperazine ring. Among all the compounds synthesized, 6d and 6l were most potent with IC50 values of 3.59 and 5.58 mu M, respectively against A549 lung cancer cells, while 5f and 6l possessed IC50 values of 3.49 and 4.57 mu M, respectively against HCT-116 colon cancer cells which were comparable to that of Sunitinib, an indolin-2-one derivative in cancer therapy. (C) 2013 Elsevier Ltd. All rights reserved.