[1,2,4]triazolo[4,3-a]phthalazine-6(5H)-one-3(2H)-thione | 324056-19-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: [1,2,4]triazolo[4,3-a]phthalazine-6(5H)-one-3(2H)-thione
• 英文别名: 3-Sulfanylidene-2,5-dihydro-[1,2,4]triazolo[3,4-a]phthalazin-6-one
• CAS: 324056-19-1
• 化学式: C₉H₆N₄OS
• 分子量: 218.239
• InChiKey: RNSRXFXCOHOCAN-UHFFFAOYSA-N

物化性质

• 熔点：
  326-328 °C(Solv: ethanol (64-17-5))
• 密度：
  1.77±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [1,2,4]triazolo[4,3-a]phthalazine-6(5H)-one-3(2H)-thione 在 四丁基氢氧化铵 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 4.66h， 生成 6-methoxy-3-methylthio-[1,2,4]triazolo[3,4-a]phthalazine
  参考文献：
  名称：

  Preparative and theoretical study on chain length-dependence and substrate selectivity in the cycloalkylation of condensed [1,2,4]triazolo[4,3-b]pyridazine-6(5H)-one-3(2H)-thiones

  摘要：

  Cyclization of condensed [1,2,4]triazolo[4,3-b]pyridazine-3(2H)-6(5H)-ones with alpha,omega-dibromoalkanes afforded a series of novel ring systems including zwitterions and isomeric tetracyclic lactams. The product distribution is controlled by the chain-length of the reagent, the polarity of the solvent and the structure of ring A in the substrate. The observed substrate selectivity was interpreted on the basis of amide-I IR frequencies and by the results of ab initio B3LYP DFr calculations carried out at 6-31 G and 6-31 G(d) basis sets using IPCM solvation model. The cycloalkylation with 1,4-dibromobutane gave also macrocyles as detectable by-products which underwent ring contraction yielding lactams on attempted chromatographic separation. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)01156-0
• 作为产物：
  描述：

  1,4-二氯酞嗪 在 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 生成 [1,2,4]triazolo[4,3-a]phthalazine-6(5H)-one-3(2H)-thione
  参考文献：
  名称：

  设计，合成，分子建模，体内研究和评估新型酞嗪衍生物作为潜在的DNA嵌入剂和拓扑异构酶II抑制剂的抗癌活​​性。

  摘要：

  在本文中，我们报告了作为Topo II抑制剂和DNA嵌入剂的一系列新的酞嗪衍生物的设计和合成。体外评价合成的化合物对HepG-2，MCF-7和HCT-116细胞系的细胞毒性活性。此外，还对Topo II抑制活性和DNA嵌入亲和力进行了研究，发现它们具有最强的活性，是抗癌活性的潜在机制。化合物15h，23c，32a，32b和33表现出对Topo II的最高活性，IC 50为5.44至8.90 µM，而化合物27和32a被认为是IC 50最有效的DNA结合剂值分别为36.02和48.30 µM。此外，化合物32a诱导HepG-2细胞凋亡，并使细胞周期停滞在G2 / M期。此外，化合物32a在2.5和5μM的浓度下显示Topo II中毒作用，并且在10μM的浓度下显示Topo II催化抑制作用。另外，化合物32b在体内显示出显着的肿瘤生长抑制作用。此外，针对DNA-Topo II复合物和DNA进

  DOI：

  10.1016/j.bioorg.2020.104233

文献信息

• Novel ring transformations of condensed [1,2,4]triazolo[4,3-b]pyridazine-6(5H)-one-3(2H)-thiones effected by dialkyl-acetylenedicarboxylates
  作者：Mónika Simó、Antal Csámpai、Veronika Harmat、Orsolya Barabás、Gábor Magyarfalvy

  DOI：10.1016/s0040-4020(01)00672-x

  日期：2001.8

  On heating with dialkyl-acetylenedicarboxylates in DMF condensed [1,2,4]-triazolo[4,3-b] pyridazine-6(5H)-one-3(2H)-thiones undergo unprecedented ring transformations yielding novel tetracyclic 1,3-diazepines and thiazolotriazole derivatives depending on the applied reaction temperature. The observed substrate selectivity was interpreted on the basis of the results of comparative theoretical calculations carried out at semiempirical level (AMI). (C) 2001 Elsevier Science Ltd. All rights reserved.
• Design, synthesis, molecular modeling, in vivo studies and anticancer activity evaluation of new phthalazine derivatives as potential DNA intercalators and topoisomerase II inhibitors
  作者：Abdel-Ghany A. El-Helby、Helmy Sakr、Rezk R. Ayyad、Hazem A. Mahdy、Mohamed M. Khalifa、Amany Belal、Mahmoud Rashed、Abdou El-Sharkawy、Ahmed M. Metwaly、Mostafa A. Elhendawy、Mohamed M. Radwan、Mahmoud A. ElSohly、Ibrahim H. Eissa

  DOI：10.1016/j.bioorg.2020.104233

  日期：2020.10

  Herein we report the design and synthesis of a new series of phthalazine derivatives as Topo II inhibitors and DNA intercalators. The synthesized compounds were in vitro evaluated for their cytotoxic activities against HepG-2, MCF-7 and HCT-116 cell lines. Additionally, Topo II inhibitory activity and DNA intercalating affinity were investigated for the most active compounds as a potential mechanism

  在本文中，我们报告了作为Topo II抑制剂和DNA嵌入剂的一系列新的酞嗪衍生物的设计和合成。体外评价合成的化合物对HepG-2，MCF-7和HCT-116细胞系的细胞毒性活性。此外，还对Topo II抑制活性和DNA嵌入亲和力进行了研究，发现它们具有最强的活性，是抗癌活性的潜在机制。化合物15h，23c，32a，32b和33表现出对Topo II的最高活性，IC 50为5.44至8.90 µM，而化合物27和32a被认为是IC 50最有效的DNA结合剂值分别为36.02和48.30 µM。此外，化合物32a诱导HepG-2细胞凋亡，并使细胞周期停滞在G2 / M期。此外，化合物32a在2.5和5μM的浓度下显示Topo II中毒作用，并且在10μM的浓度下显示Topo II催化抑制作用。另外，化合物32b在体内显示出显着的肿瘤生长抑制作用。此外，针对DNA-Topo II复合物和DNA进
• Preparative and theoretical study on chain length-dependence and substrate selectivity in the cycloalkylation of condensed [1,2,4]triazolo[4,3-b]pyridazine-6(5H)-one-3(2H)-thiones
  作者：Antal Csámpai、Mónika Simó、Zoltán Szlávik、András Kotschy、Gábor Magyarfalvi、György Túrós

  DOI：10.1016/s0040-4020(02)01156-0

  日期：2002.10

  Cyclization of condensed [1,2,4]triazolo[4,3-b]pyridazine-3(2H)-6(5H)-ones with alpha,omega-dibromoalkanes afforded a series of novel ring systems including zwitterions and isomeric tetracyclic lactams. The product distribution is controlled by the chain-length of the reagent, the polarity of the solvent and the structure of ring A in the substrate. The observed substrate selectivity was interpreted on the basis of amide-I IR frequencies and by the results of ab initio B3LYP DFr calculations carried out at 6-31 G and 6-31 G(d) basis sets using IPCM solvation model. The cycloalkylation with 1,4-dibromobutane gave also macrocyles as detectable by-products which underwent ring contraction yielding lactams on attempted chromatographic separation. (C) 2002 Elsevier Science Ltd. All rights reserved.