3-amino-1-(3-fluorophenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile | 1443004-18-9

• 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-(3-fluorophenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
• 英文别名: 3-amino-1-(3-fluorophenyl)-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
• CAS: 1443004-18-9
• 化学式: C₁₈H₁₁FN₄O₂
• 分子量: 334.309
• InChiKey: OQORMJDAODOMSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 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：
  90.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-1-(3-fluorophenyl)-5,10-dihydro-5,10-dioxo-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80%的产率得到15-amino-14-(3-fluorophenyl)-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：

  苯酐 、 丙二腈 、 3-氟苯甲醛 在 copper(II) acetate monohydrate 、 一水合肼 作用下， 以 neat (no solvent) 为溶剂， 反应 5.0h， 以89%的产率得到3-amino-1-(3-fluorophenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
  参考文献：
  名称：

  乙酸铜（II）一水合物：一种高效，环保的催化剂，可在溶剂-下单锅多组分合成生物活性螺吡喃和1 H-吡唑并[1,2-b]邻苯二甲-5,10-二酮衍生物。自由条件

  摘要：

  摘要 我们已经研究了乙酸铜（II）一水合物作为温和的，对环境无害的，天然的和经济的催化剂，用于多组分有效合成生物活性spiro-4 H -pyran衍生物和1 H -pyrazolo的催化能力[1,2] -b] phthalazine-5,10-dione衍生物，具有优异的收率和较短的反应时间。该方法最重要的优点是其温和，无毒且便宜的催化剂，一锅合成，环境友好的性质，无溶剂条件，简单的操作程序和高效的条件。 图形概要

  DOI：

  10.1007/s11164-016-2565-0

文献信息

• 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。
• InCl3-catalyzed green synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones under solvent-free conditions
  作者：Mudumala Veeranarayana Reddy、Yeon Tae Jeong

  DOI：10.1016/j.tetlet.2013.04.109

  日期：2013.7

  A simple, efficient, and green practical approach to 1H-pyrazolo[1,2-b]phthalazine-5,10-diones from phthalhydrazide, aldehydes, and malononitrile/ethyl cyanoacetate has been developed that uses inexpensive and readily available InCl3 as a catalyst in solvent-free one-pot three-component cyclo condensation reaction. This method should provide high yields, shorter reaction time, easy work-up, purification

  已开发出一种简单，有效且绿色的实用方法，用于从邻苯二甲酰肼，醛和丙二腈/氰基乙酸乙酯中合成1 H-吡唑并[1,2- b ]邻苯二甲-5,10-二酮，使用廉价且易得的InCl 3作为无溶剂一锅三组分环缩合反应中的催化剂。该方法应提供高收率，较短的反应时间，易于后处理，通过非色谱法纯化产物以及更清洁的反应。这是N-稠合杂环合成的新策略，在有机和药物化学中具有更广泛的应用。
• Silica gel-supported tungstic acid (STA): A new, highly efficient and recyclable catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates under neat conditions
  作者：M. Veeranaryana Reddy、P. Chenna Rohini Kumar、G. Chandra Sekhar Reddy、C. Suresh Reddy

  DOI：10.1016/j.crci.2014.01.026

  日期：2014.12

  Résumé 1H-Pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates possess a broad range of applications as active compounds in the pharmacological and biological fields. We developed an efficient and ecofriendly silica gel-supported tungstic acid (STA)-catalyzed one-pot synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione carbonitriles and carboxylates by a three-component reaction of an aldehyde, a malononitrile/ethyl cyanoacetate and a phthalhydrazide under solvent-free conditions. The major advantages of the present method are experimental simplicity, use of an inexpensive and ecofriendly reusable catalyst, good yields, and short reaction times.

  摘要 1H-吡唑[1,2-b]佛尔马嗪-5,10-二酮亚硝基化合物和羧酸盐在药理学和生物学领域作为活性化合物具有广泛的应用。我们开发了一种高效且环保的硅胶载体钨酸（STA）催化一锅法合成1H-吡唑[1,2-b]佛尔马嗪-5,10-二酮亚硝基化合物和羧酸盐的方法，该方法通过醛、马龙腈/乙基氰代乙酸和佛尔马嗪在无溶剂条件下进行三组分反应。本方法的主要优点在于实验简单、使用廉价且环保的可重复使用催化剂、产率良好以及反应时间短。
• Caesium carbonate supported on hydroxyapatite-encapsulated Ni_0.5 Zn_0.5 Fe₂ O₄ nanocrystallites as a novel magnetically basic catalyst for the one-pot synthesis of pyrazolo[1,2-b]phthalazine-5,10-diones
  作者：Behrooz Maleki、Samaneh Barat Nam Chalaki、Samaneh Sedigh Ashrafi、Esmail Rezaee Seresht、Farid Moeinpour、Amir Khojastehnezhad、Reza Tayebee

  DOI：10.1002/aoc.3288

  日期：2015.5

  A novel nanomagnetic basic catalyst of caesium carbonate supported on hydroxyapatite‐coated Ni0.5Zn0.5Fe2O4 magnetic nanoparticles (Ni0.5Zn0.5Fe2O4@HAP‐Cs2CO3) was prepared. This new catalyst was fully characterized using Fourier transform infrared spectroscopy, transmission and scanning electron microscopy, X‐ray diffraction and vibrating sample magnetometry techniques, and then the catalytic activity

  制备了负载在羟基磷灰石包覆的Ni 0.5 Zn 0.5 Fe 2 O 4磁性纳米粒子（Ni 0.5 Zn 0.5 Fe 2 O 4 @ HAP-Cs 2 CO 3）上的碳酸铯新型纳米磁性碱性催化剂。使用傅立叶变换红外光谱，透射和扫描电子显微镜，X射线衍射和振动样品磁强分析技术对这种新型催化剂进行了充分表征，然后研究了该催化剂在1 H吡唑啉的合成中的催化活性[1,2]。 -b]酞嗪-5,10-二酮衍生物。另外，Ni 0.5 Zn0.5 Fe 2 O 4 @ HAP-Cs 2 CO 3可以重复使用至少五次，而不会显着降低活性，并且可以通过施加外部磁体轻松地进行回收。因此，开发的纳米磁性催化剂潜在地可用于绿色经济地生产有机化合物。版权所有©2015 John Wiley＆Sons，Ltd.
• Saccharin: a green, economical and efficient catalyst for the one-pot, multi-component synthesis of 3,4-dihydropyrimidin-2-(1H)-one derivatives and 1H-pyrazolo [1,2-b] phthalazine-5,10-dione derivatives and substituted dihydro-2-oxypyrrole
  作者：Farzaneh Mohamadpour、Malek Taher Maghsoodlou、Reza Heydari、Mojtaba Lashkari

  DOI：10.1007/s13738-016-0871-5

  日期：2016.8

  purification steps and eco-friendly. Graphical AbstractWe have studied the catalytic ability of saccharin as a green, economical and environmentally benign nature for the multi-component efficient synthesis of 3,4-dihydropyrimidin-2-(1H)-ones derivatives, 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives and substituted dihydro-2-oxypyrrole with excellent yields and short reaction times. Green catalyst

  摘要在这种方法中，我们报道了糖精作为绿色，环保的多组分有效合成3,4-二氢嘧啶-2-（1 H）-one衍生物和1 H -pyrazolo的催化剂的催化能力[1 ，2 - b ]酞嗪-5，10-二酮衍生物和取代的二氢-2-氧基吡咯具有优异的产率和较短的反应时间。本发明的方法具有显着的优点，例如绿色，廉价且无毒的催化剂，一锅法，环境友好的性质，无溶剂条件，操作简便，无需色谱纯化步骤以及对环境友好。 图形概要我们已经研究了糖精作为绿色，经济和环境友好性质对多组分有效合成3,4-dihydropyrimidin-2-（1 H）-ones衍生物1 H -pyrazolo [1,2- b ]酞嗪5,10-二酮衍生物和取代的二氢-2-氧基吡咯，具有优异的收率和较短的反应时间。绿色催化剂，温和，无毒，廉价，操作简单，一锅法，高催化活性，生态友好，易于从反应混合物中分离，无需柱色谱即可一锅多组分合成这些化合物此程序最重要的优点。