3-amino-1-(2-methoxyphenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile | 1384462-33-2

• 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-(2-methoxyphenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
• 英文别名: 3-amino-1-(2-methoxyphenyl)-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
• CAS: 1384462-33-2
• 化学式: C₁₉H₁₄N₄O₃
• 分子量: 346.345
• InChiKey: XFBIAQKLLZSZRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  99.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-1-(2-methoxyphenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile 、 环己酮 在 aluminum (III) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 24.0h， 以75%的产率得到15-amino-14-(2-methoxyphenyl)-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：

  邻苯二甲酸亚胺 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 3-amino-1-(2-methoxyphenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
  参考文献：
  名称：

  介绍了一种高通量纳米催化方法，利用二氧化硅包覆的纳米珍珠岩负载的咪唑鎓基离子液体作为一种新型、可重复使用且环保的纳米催化剂，在绿色条件下合成一些吡唑并酞嗪衍生物

  摘要：

  开发了一种高通量离子液体催化体系作为一种新型高效且可重复使用的多相纳米催化剂，用于在78℃乙醇中一锅合成一些1H-吡唑并[1,2-b]酞嗪-5,10-二酮。合成了设计的纳米催化剂，然后通过傅里叶变换红外光谱（FTIR）、能量色散X射线、透射电子显微镜、场发射扫描电子显微镜等表征其功能、组成、尺寸、形态、表面性质和晶体尺寸， Brunauer-Emmett-Teller 和 X 射线衍射技术。在此方案中，目标产物获得了高至优异的产率 (80-96%)。所有合成产物的结构均通过氢核磁共振( 1 H NMR) 和FT-IR 光谱确定。这种环境友好的方法具有反应过程清洁、催化剂用量少、反应条件温和、溶剂环境友好、反应时间短、产品收率高至优异等优点。此外，珍珠岩NPs/SiO 2 /IL在六次循环使用后催化活性没有明显损失。此外，热过滤研究的结果表明，催化剂表面没有发生浸出，证明了珍珠岩纳米粒子/SiO

  DOI：

  10.1007/s11164-024-05234-4

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
• One-pot green synthesis of novel 5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine derivatives with eco-friendly biodegradable eggshell powder as efficacious catalyst
  作者：Nagaraju Kerru、Lalitha Gummidi、Sandeep V. H. S. Bhaskaruni、Surya Narayana Maddila、Sreekantha B. Jonnalagadda

  DOI：10.1007/s11164-020-04135-6

  日期：2020.6

  Abstract An eco-friendly and efficient green protocol is developed for the synthesis of sixteen pyrazolo-phthalazine derivatives (5a–p) by using inexpensive biodegradable eggshell powder (ESP) as a heterogeneous catalyst. The four-component one-pot condensation reaction proceeded through Knoevenagel–Michael reaction of different chosen active methylene compounds, phthalic anhydride, and hydrazine hydride

  摘要 开发了一种生态友好且高效的绿色方案，用于合成十六种吡唑并-酞嗪衍生物（5a–p），方法是使用廉价的可生物降解蛋壳粉（ESP）作为非均相催化剂。四组分一锅式缩合反应是通过在60°C的水中不同选择的活性亚甲基化合物，邻苯二甲酸酐和肼氢化物与各种取代的芳族醛进行的Knoevenagel–Michael反应进行的，提供了高收率的产品（93 –98％）在28至45分钟的快速反应时间内。该材料采用不同的分析技术（SEM，TEM，XRD，BET和FT-IR）表征，并且由高百分比的氧化钙和碳酸盐以及较少百分比的Na和Mg元素组成（基于EDX分析） 。ESP材料显示出可回收性（4倍），而催化效率没有任何明显的损失。除了， 图形摘要
• Mild preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives with magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane as catalyst under ambient and solvent-free conditions
  作者：Hamid Reza Shaterian、Majid Mohammadnia

  DOI：10.1007/s11164-012-0969-z

  日期：2014.1

  An efficient, one-pot quantitative procedure for preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives from four-component condensation reaction of hydrazine monohydrate, phthalic anhydride, malononitrile or ethyl cyanoacetate, and aromatic aldehydes in the presence of magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane as catalyst under mild, ambient, and solvent-free conditions is described. Simple procedure, high yield, short reaction time, and environmentally benign method are advantages of this protocol. The magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane can be recovered and reused several times without loss of activity.

  描述了一种高效的一锅法定量制备1H-吡唑并[1,2-b]酞嗪-5,10-二酮衍生物的方法，该方法通过水合肼、邻苯二甲酸酐、丙二腈或氰乙酸乙酯与芳香醛在磁性Fe3O4纳米粒子（表面包覆有(3-氨丙基)-三乙氧基硅烷）催化下进行四组分缩合反应，条件温和、环境、无溶剂。该方案的优点是操作简单、产率高、反应时间短、环境友好。磁性 纳米粒子（表面包覆有(3-氨丙基)-三乙氧基硅烷）可回收并重复使用多次而不会丧失活性。
• 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。
• New role for photoexcited organic dye, Na2 eosin Y via the direct hydrogen atom transfer (HAT) process in photochemical visible-light-induced synthesis of spiroacenaphthylenes and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones under air atmosphere
  作者：Farzaneh Mohamadpour

  DOI：10.1016/j.dyepig.2021.109628

  日期：2021.10

  A green multi-component tandem strategy for metal-free synthesizing spiroacenaphthylenes and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones by Knoevenagel-Michael cyclocondensation is reported via organic dye Na2 eosin Y-derived photoexcited states functions as a direct hydrogen atom transfer (HAT) catalyst via visible light-mediated in aqueous ethyl lactate at ambient temperature under air atmosphere.

  通过有机染料 Na 2曙红 Y 衍生的光激发态，通过Knoevenagel-Michael 环缩合反应无金属合成螺苊和 1 H-吡唑并[1,2 - b ]酞嗪-5,10-二酮的绿色多组分串联策略在环境温度和空气气氛下，通过可见光介导的乳酸乙酯水溶液作为直接氢原子转移 (HAT) 催化剂。这项研究为进一步使用具有商业可用性和廉价性的无金属有机染料 Na 2曙红Y在光化学合成中使用最少的催化剂，能源效率高，收率高，操作简单，反应省时，原子经济性高，从而满足可持续和绿色化学的一些特征。值得注意的是，这种环化反应也可以在克级规模上运行，这凸显了该反应在工业用途中的潜力。