3-amino-1-(4-nitrophenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile

• 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: 3-amino-1-(4-nitrophenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
• 英文别名: 3-amino-5,10-dihydro-1-(4-nitrophenyl)-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile；3-amino-1-(4-nitrophenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b] phthalazine-2-carbonitrile；3-amino-1-(4-nitrophenyl)-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
• 化学式: C₁₈H₁₁N₅O₄
• 分子量: 361.316
• InChiKey: RHIJDEHPTXACID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  环己酮 、 3-amino-1-(4-nitrophenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile 在 aluminum (III) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 24.0h， 以80%的产率得到15-amino-14-(4-nitrophenyl)-2,3,4,14-tetrahydro-1H-quinolino[2',3':3,4]pyrazolo[1,2-b]phthalazine-7,12-dione
  参考文献：
  名称：

  New racemic annulated pyrazolo[1,2-b]phthalazines as tacrine-like AChE inhibitors with potential use in Alzheimer's disease

  摘要：

  A novel series of tacrine-like compounds 7a-u possessing a fused pyrazolo[1,2-b]phthalazine structure were designed and synthesized as potent and selective inhibitors of AChE. The in-vitro biological assessments demonstrated that several compounds had high anti-AChE activity at nano-molar level. The more promising compound 71 with IC50 of 49 nM was 7-fold more potent than tacrine and unlike tacrine, it was highly selective against AChE over BuChE. The cell-based assays against hepatocytes (HepG2) and neuronal cell line (PC12) revealed that 71 had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in PC12 cells. This compound could also inhibit AChE-induced and self-induced A beta peptide aggregation. The advantages including synthetic accessibility, high potency and selectivity, low toxicity, adjunctive neuroprotective and A beta aggregation inhibitory activity, make this compound as a new multifunctional lead for Alzheimer's disease drug discovery. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.072
• 作为产物：
  描述：

  邻苯二酰胺 在 hydrazine hydrate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 0.6h， 生成 3-amino-1-(4-nitrophenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
  参考文献：
  名称：

  H4 [W12SiO40]的纳米磁异化反应：用于1H-吡唑并[1,2-b]邻苯二甲二酮衍生物的合成

  摘要：

  我们方便地在氨基官能化的硅磁铁矿纳米粒子上涂覆硅钨酸（STA，H 4 [W 12 SiO 40 ]），因为磁性纳米粒子的表面官能化是绿色高效催化的绝佳方法。使用各种技术对纳米颗粒进行结构表征。通过合成1 H –吡唑并[1,2- b]探测了STA-胺-Si-磁铁矿纳米颗粒的催化活性和可回收性]酞嗪二酮衍生物。反应平稳进行，以优异的产率和短的反应时间提供产物。可以使用简单的外部磁体轻松回收催化剂，并重复使用几次，而不会造成活性的任何损失。在此，我们报告了作为均相和非均相催化剂的H 4 [W 12 SiO 40 ]的活性的比较，发现后者更为有效。这些发现为吡唑并[1,2- b ]邻苯二甲腈二酮衍生物的环境友好合成提供了有效的方法。

  DOI：

  10.1002/aoc.4001

文献信息

• Mono- and bis-pyrazolophthalazines: Design, synthesis, cytotoxic activity, DNA/HSA binding and molecular docking studies
  作者：Mahdia Hamidinasab、Alieh Ameri、Azadeh Hekmat、Hamid Forootanfar、Tohid Mortezazadeh、Mohammad Ali Bodaghifard、Fariba Peytam、Rezvan Esmaeili、Alireza Foroumadi、Mohammad Sharifzadeh、Akbar Mobinikhaledi、Mehdi Khoobi

  DOI：10.1016/j.bmc.2020.115944

  日期：2021.1

  indicating interaction of the compounds with the secondary structure of HSA and significant change of DNA conformation, presumably via a groove binding mechanism. Additionally, molecular docking and site-selective binding studies confirmed the fundamental interaction of compounds 4e and 6c with base pairs of DNA. Compounds 4e and 6c showed promising features to be considered as potential lead structures for

  为了寻找新的有效细胞毒性化合物，通过有效的一锅三组分和伪五组分合成方法合成了几种单-和双-吡唑并酞嗪4a-m和6a-h。评估了所有衍生物对四种人类癌细胞系 A549、HepG2、MCF-7 和 HT29 的体外细胞毒活性。化合物4e对正常细胞系（MRC-5 和 MCF 10A，IC 50  > 200 µM）表现出低毒性，对 A549 细胞系显示出优异的细胞毒活性，IC 50值为 1.25 ± 0.19 µM，是阿霉素的 1.8 倍（ IC 50  = 2.31 ± 0.13 µM）。此外，化合物6c对 A549 和 MCF-7 细胞系表现出显着的细胞毒活性（IC 50  = 1.35 ± 0.12 和 0.49 ± 0.01 µM，分别），比阿霉素高两倍以上。最佳活性单-和双-吡唑并酞嗪（4e和6c）与 HSA 和 DNA的结合特性通过各种技术进行了全面评估，包括 UV-Vis 吸收、圆二色性
• Nano-ZnO: an efficient and reusable catalyst for one-pot synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones and pyrazolo[1,2-a][1,2,4]triazole-1,3-diones
  作者：Ali Azarifar、Razieh Nejat-Yami、Davood Azarifar

  DOI：10.1007/s13738-012-0159-3

  日期：2013.4

  nano-structured ZnO has been explored in the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione and pyrazolo[1,2-a][1,2,4]triazole-1,3-dione derivatives via a three-component coupling reaction between aromatic aldehydes, malononitrile, and phthalhydrazides or 4-arylurazoles, respectively. High yield, low reaction times, non-toxicity and recyclability of the catalyst, and easy work-up are the main merits

  摘要在1 H-吡唑并[1,2-b]酞嗪-5,10-二酮和吡唑并[1,2-a] [1,2,4]三唑的合成中探索了纳米结构ZnO的催化活性。-1,3-二酮衍生物分别通过芳族醛，丙二腈和邻苯二甲酰肼或4-芳基脲唑之间的三组分偶联反应形成。该方案的主要优点是高收率，低反应时间，无毒，催化剂可回收利用，易于后处理。 图形概要
• Ultrasound-assisted synthesis of pyrazolo[1,2-b]phthalazines and dihydrospiro[indoline-3,1'-pyrazolo[1,2-b]phthalazines] using TBAF as an efficient phase-transfer catalyst
  作者：H. Kefayati、A. Delafrooz、S. Homayoon

  DOI：10.1134/s107036321607032x

  日期：2016.7

  Tetrabutylammonim fluoride has been used as an efficient catalyst for synthesis of pyrazolo[1,2-b]-phthalazine-5,10-diones and dihydrospiro[indoline-3,1'-pyrazolo[1,2-b]phthalazines] by one-pot three-component reaction of phthalhydrazide, aromatic aldehydes or isatin derivatives, with malononitrile in water under ultrasond irradiation. This rapid method gave the products in high yield.

  四丁基氟化铵已被用作合成吡唑并[1,2 - b ]-酞嗪-5,10-二酮和二氢螺并[吲哚啉-3,1'-吡唑并[1,2- b ]酞嗪的有效催化剂。超声波照射下，邻苯二甲酰肼，芳香醛或靛红衍生物与丙二腈的三锅反应。这种快速的方法以高收率获得了产物。
• Preparation of 1<i>H</i>-pyrazolo[1,2-<i>b</i>]phthalazine-5,10-diones using ZrO₂ nanoparticles as a catalyst under solvent-free conditions
  作者：Mohammad Piltan

  DOI：10.1515/hc-2017-0142

  日期：2017.10.26

  Abstract Zirconium oxide nanoparticles are an efficient catalyst for the preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones via a three-component reaction of phthalhydrazide, aromatic aldehydes and malononitrile under solvent-free conditions.

  摘要 氧化锆纳米颗粒是一种有效的催化剂，可在无溶剂条件下通过邻苯二甲酰肼、芳香醛和丙二腈的三组分反应制备 1H-吡唑并[1,2-b]酞嗪-5,10-二酮。
• Nano Brönsted solid acid containing double-charged diazoniabi-cyclo[2.2.2]octane chloride supported on nano rice husk silica: an efficient catalyst for the one-pot synthesis of phthalazine compounds
  作者：Jamal Davarpanah、Ali Reza Kiasat

  DOI：10.1039/c4ra13263g

  日期：——

  (TGA-DTG), and Brunauer–Emmett–Teller (BET) measurements. The catalytic activity of this nanocomposite was successfully tested through the one-pot synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones via three-component couplings of phthalhydrazide, aromatic aldehydes, and malononitrile. The heterogeneous catalyst could be recovered easily and reused without significant loss of its catalytic activity

  在目前的工作中，从低成本稻壳灰（RH-SiO 2）合成了无定形二氧化硅纳米粒子。纳米粒子随后通过溶胶-凝胶法（RH @ [SiPrDABCO @ BuSO 3 H] HSO 4）用含有双电荷的重氮二氮杂双环[2.2.2]辛烷的酸性离子液体改性。通过傅立叶变换红外光谱（FT-IR），扫描电子显微镜（SEM），热重分析-导数热重分析（TGA-DTG）和Brunauer-Emmett-Teller（BET）对这一布朗斯台德固体酸的结构性质进行了系统研究） 测量。通过一锅合成1 H-吡唑并[1,2- b]成功地测试了该纳米复合材料的催化活性。通过邻苯二甲酰肼，芳族醛和丙二腈的三组分偶联反应制得] phthalazine-5,10-diones 。该多相催化剂可以容易地回收和再利用而不会显着损失其催化活性。