6-(4-(2-fluorophenyl)piperazine-1-yl)-3(2H)-pyridazinone | 756901-39-0

• 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: 6-(4-(2-fluorophenyl)piperazine-1-yl)-3(2H)-pyridazinone
• 英文别名: 6-[4-(2-Fluorophenyl)piperazin-1-yl]-3(2h)-pyridazinone；3-[4-(2-fluorophenyl)piperazin-1-yl]-1H-pyridazin-6-one
• CAS: 756901-39-0
• 化学式: C₁₄H₁₅FN₄O
• 分子量: 274.298
• InChiKey: VZTQEKBRCTYWJV-UHFFFAOYSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-(2-fluorophenyl)piperazine-1-yl)-3(2H)-pyridazinone 在 potassium carbonate 、 一水合肼 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 3.0h， 生成 3-[3-[4-(2-Fluorophenyl)piperazin-1-yl]-6-oxopyridazin-1-yl]propanehydrazide
  参考文献：
  名称：

  Oezcelik, Azime Berna; Goekce, Mehtap; Orhan, Ilkay, Arzneimittel-Forschung/Drug Research, 2010, vol. 60, # 7, p. 452 - 458

  摘要：

  DOI：
• 作为产物：
  描述：

  1-(2-氟苯基)哌嗪 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 6-(4-(2-fluorophenyl)piperazine-1-yl)-3(2H)-pyridazinone
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors

  摘要：

  设计、合成和评估了含有(2-氟苯基)哌嗪基团的十二种吡啶并嗪酮(T1-T12)，用于单胺氧化酶(MAO)-A和-B的抑制活性。发现T6是最强的MAO-B抑制剂，IC50值为0.013 µM，其次是T3 (IC50 = 0.039 µM)。对于MAO-B的抑制效力，通过间位溴取代 (T6) 比对位溴取代 (T7) 更增强。对于对位取代，MAO-B的抑制效力如下：-Cl (T3) > -N(CH3)2 (T12) > -OCH3 (T9) > Br (T7) > F (T5) > -CH3 (T11) > -H (T1)。T6和T3有效抑制MAO-A，IC50值分别为1.57和4.19 µM，并且对MAO-B具有最高的选择性指数(SIs) (分别为120.8和107.4)。T3和T6被发现是MAO-B的可逆和竞争性抑制剂，其Ki值分别为0.014和0.0071。此外，T6对健康成纤维细胞(L929)的毒性较T3低。与MAO结合位点的分子对接模拟显示，T6和T3在与MAO-B的对接评分高于与MAO-A。这些结果表明，T3和T6是MAO-B的选择性、可逆和竞争性抑制剂，应被视为治疗像阿尔茨海默病这样的神经退行性疾病的首要候选药物。

  DOI：

  10.3390/molecules25225371

文献信息

• Synthesis of New 6-[4-(2-Fluorophenylpiperazine-1-YL)]-3(2H)-Pyridazinone-2-Acethyl-2- (Substitutedbenzal)Hydrazone Derivatives and Evulation of Their Cytotoxic Effects in Liver and Colon Cancer Cell Lines
  作者：Zeynep Özdemir、Neşe Başak-Türkmen、İdris Ayhan、Osman Çiftçi、Mehtap Uysal

  DOI：10.1007/s11094-019-01927-y

  日期：2019.2.15

  In this study, seven new 3(2H)-pyridazinone derivatives expected to show cytotoxic activity in liver and colon cancer cell lines were synthesized. Their structures were confirmed by the IR, 1H-NMR, 13C-NMR spectra and elementary analyses. Compunds V1-V7 were tested on HEP3B (liver cancer) and HTC116 (colon cancer) cell lines for cytotoxicity by using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium] proliferation assay. Human fibroblast cells were used as safety control in these tests. 6-[4-(2-Fluorophenyl)piperazine-1-yl]-3(2H)-pyridazinone-2-acetyl-2-(2-chlorobenzal)hydrazone (compound V3 ) was the most active agent with respect to HEP3B and HTC116 cell lines.

  在这项研究中，合成了七种新型的3(2H)-吡嗪酮衍生物，预计它们在肝癌和结肠癌细胞系中具有细胞毒活性。它们的结构通过红外光谱、氢谱、碳谱和元素分析得到了确认。化合物V1-V7在HEP3B（肝癌）和HTC116（结肠癌）细胞系中进行了细胞毒性测试，使用了MTS [3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺酰苯基)-2H-四氮唑]增殖测定法。这些测试中，使用人纤维母细胞作为安全对照。6-[4-(2-氟苯基)哌嗪-1-基]-3(2H)-吡嗪酮-2-乙酰基-2-(2-氯苄)肼 (化合物V3) 是对HEP3B和HTC116细胞系最活跃的药物。
• Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors
  作者：Muhammed Çeçen、Jong Min Oh、Zeynep Özdemir、Saliha Ebru Büyüktuncel、Mehtap Uysal、Mohamed A. Abdelgawad、Arafa Musa、Nicola Gambacorta、Orazio Nicolotti、Bijo Mathew、Hoon Kim

  DOI：10.3390/molecules25225371

  日期：——

  Twelve pyridazinones (T1–T12) containing the (2-fluorophenyl) piperazine moiety were designed, synthesized, and evaluated for monoamine oxidase (MAO) -A and -B inhibitory activities. T6 was found to be the most potent MAO-B inhibitor with an IC50 value of 0.013 µM, followed by T3 (IC50 = 0.039 µM). Inhibitory potency for MAO-B was more enhanced by meta bromo substitution (T6) than by para bromo substitution (T7). For para substitution, inhibitory potencies for MAO-B were as follows: -Cl (T3) > -N(CH3)2 (T12) > -OCH3 (T9) > Br (T7) > F (T5) > -CH3 (T11) > -H (T1). T6 and T3 efficiently inhibited MAO-A with IC50 values of 1.57 and 4.19 µM and had the highest selectivity indices (SIs) for MAO-B (120.8 and 107.4, respectively). T3 and T6 were found to be reversible and competitive inhibitors of MAO-B with Ki values of 0.014 and 0.0071, respectively. Moreover, T6 was less toxic to healthy fibroblast cells (L929) than T3. Molecular docking simulations with MAO binding sites returned higher docking scores for T6 and T3 with MAO-B than with MAO-A. These results suggest that T3 and T6 are selective, reversible, and competitive inhibitors of MAO-B and should be considered lead candidates for the treatment of neurodegenerative disorders like Alzheimer’s disease.

  设计、合成和评估了含有(2-氟苯基)哌嗪基团的十二种吡啶并嗪酮(T1-T12)，用于单胺氧化酶(MAO)-A和-B的抑制活性。发现T6是最强的MAO-B抑制剂，IC50值为0.013 µM，其次是T3 (IC50 = 0.039 µM)。对于MAO-B的抑制效力，通过间位溴取代 (T6) 比对位溴取代 (T7) 更增强。对于对位取代，MAO-B的抑制效力如下：-Cl (T3) > -N(CH3)2 (T12) > -OCH3 (T9) > Br (T7) > F (T5) > -CH3 (T11) > -H (T1)。T6和T3有效抑制MAO-A，IC50值分别为1.57和4.19 µM，并且对MAO-B具有最高的选择性指数(SIs) (分别为120.8和107.4)。T3和T6被发现是MAO-B的可逆和竞争性抑制剂，其Ki值分别为0.014和0.0071。此外，T6对健康成纤维细胞(L929)的毒性较T3低。与MAO结合位点的分子对接模拟显示，T6和T3在与MAO-B的对接评分高于与MAO-A。这些结果表明，T3和T6是MAO-B的选择性、可逆和竞争性抑制剂，应被视为治疗像阿尔茨海默病这样的神经退行性疾病的首要候选药物。
• Synthesis and Analgesic and Antiinflammatory Activity of Methyl 6-Substituted-3(2H)-pyridazinone-2-ylacetate Derivatives
  作者：M. F. Şahina、B. Badıçoglu、M. Gökçe、E. Küpeli、E. Yeşilada

  DOI：10.1002/ardp.200400896

  日期：2004.8

  reference nonsteroidal anti‐inflammatory drugs. Methyl 6‐(4‐(4‐fluorophenyl)piperazine)‐3(2H)‐pyridazinone‐2‐ylacetate 9e was found to be more active than acetylsalicylic acid (ASA). Methyl 6‐(4‐(2‐ethoxyphenyl)piperazine)‐3(2H)‐pyridazinone‐2‐ylacetate 9c has shown an anti‐inflammatory activity as compared to the standard compound indometacin at the carrageenan‐induced paw edema method.

  合成了一系列甲基6-取代-3(2H)-哒嗪酮-2-乙酰乙酸酯9，并在苯基苯醌诱导的扭体试验（PBQ试验）和角叉菜胶诱导的爪水肿法中评估了它们的镇痛和抗炎作用，分别。检查了化合物对胃粘膜的副作用。与参考非甾体抗炎药相比，没有一种化合物显示出胃溃疡作用。发现 6-(4-(4-氟苯基)哌嗪)-3(2H)-哒嗪酮-2-基乙酸酯 9e 比乙酰水杨酸 (ASA) 更具活性。与标准化合物吲哚美辛相比，6-(4-(2-乙氧基苯基)哌嗪)-3(2H)-哒嗪酮-2-基乙酸酯 9c 在角叉菜胶诱导的爪水肿方法中显示出抗炎活性。
• Duendar, Yasemin; Goekce, Mehtap; Kuepeli, Esra, Arzneimittel-Forschung/Drug Research, 2007, vol. 57, # 12, p. 777 - 781
  作者：Duendar, Yasemin、Goekce, Mehtap、Kuepeli, Esra、Sahin, Mustafa Fethi

  DOI：——

  日期：——
• Goekce, Mehtap; Sahin, Mustafa Fethi; Kuepeli, Esra, Arzneimittel-Forschung/Drug Research, 2004, vol. 54, # 7, p. 396 - 401
  作者：Goekce, Mehtap、Sahin, Mustafa Fethi、Kuepeli, Esra、Yesilada, Erdem

  DOI：——

  日期：——