ethyl (6-[4-(4-chlorophenyl)piperazine]-3(2H)-pyridazinone-2-yl)acetate | 1009566-97-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (6-[4-(4-chlorophenyl)piperazine]-3(2H)-pyridazinone-2-yl)acetate
• 英文别名: ethyl 6-(4-(4-chlorophenyl)piperazine-1-yl)-3(2H)-pyridazinone-2-ylacetate；Ethyl 2-(3-(4-(4-chlorophenyl)piperazin-1-yl)-6-oxopyridazin-1(6h)-yl)acetate；ethyl 2-[3-[4-(4-chlorophenyl)piperazin-1-yl]-6-oxopyridazin-1-yl]acetate
• CAS: 1009566-97-5
• 化学式: C₁₈H₂₁ClN₄O₃
• 分子量: 376.843
• InChiKey: JEAMLCLSFOFJPO-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：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  65.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (6-[4-(4-chlorophenyl)piperazine]-3(2H)-pyridazinone-2-yl)acetate 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以81%的产率得到6-(4-(4-chlorophenyl)piperazine-1-yl)-3(2H)-pyridazinone-2-ylacetohydrazide
  参考文献：
  名称：

  一些哒嗪酮衍生物作为选择性人单胺氧化酶 B 抑制剂的合成、分子建模和生物活性。

  摘要：

  背景技术由于脑神经递质水平与多种神经变性疾病如帕金森和阿尔茨海默病的病理学相关，单胺氧化酶（MAO）在平衡大脑中的这些神经递质方面起着关键作用。MAO 亚型似乎是开发中枢神经系统药物的有希望的药物靶点。哒嗪酮类具有广泛的生物活性。在这里，合成了六种哒嗪酮衍生物，并通过分子对接研究、计算机模拟 ADME 预测和体外生物筛选试验评估了它们的人单胺氧化酶抑制活性。方法通过不同哌嗪衍生物与3(2H)-哒嗪酮环反应合成化合物，并研究其对MAO的抑制作用。对接研究使用 Maestro11.8 软件进行。结果除化合物4f外，大多数合成的化合物选择性抑制hMAO-B。化合物 4a-4e 以竞争模式选择性和可逆地抑制 hMAO-B。发现化合物 4b 是该系列中最有效 (ki = 0.022 ± 0.001 µM) 和选择性 (SI (Ki hMAO-A/hMAO-B) = 206.82) hMAO-B 抑制

  DOI：

  10.1007/s43440-020-00070-w
• 作为产物：
  描述：

  1-(4-氯苯基)哌嗪 在 potassium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 12.0h， 生成 ethyl (6-[4-(4-chlorophenyl)piperazine]-3(2H)-pyridazinone-2-yl)acetate
  参考文献：
  名称：

  The Novel Synthesized Pyridazinone Derivates had the Antiproliferative and Apoptotic Effects in SHSY5Y and HEP3B Cancer Cell Line

  摘要：

  这是一篇关于研究新型吡啶嗪酮衍生物抗癌活性的论文摘要,我将其翻译如下: 背景：脑癌(神经母细胞瘤)和肝癌(肝细胞癌)是全球常见的癌症类型,目前尚无根治性治疗方法。 目标：本研究合成了5种在2位含有苯甲酰肼基团的新型吡啶嗪酮衍生物,并评估了它们对神经母细胞瘤、肝细胞癌(SHSY5Y和HEP3B)和人成纤维细胞(HF)细胞系的细胞毒性活性。本研究旨在确定这5种新型吡啶嗪酮衍生物对上述细胞系的抗增殖活性。 方法：通过6-[4-(苯基/4-氯苯基)哌嗪-1-基]-3(2H)-吡啶嗪酮-2-基乙酰肼与苯甲醛在乙醇中反应合成目标化合物。采用MTT法测定体外抗增殖活性。通过RT-PCR分析检测Bax、Bcl-2和Casp3基因表达水平。 结果：化合物4在SHSY5Y和HEP3B细胞中显示出最低的IC50值。1-5号化合物治疗导致癌细胞中Bax、Bcl-2和Casp3基因表达水平发生变化,表明细胞凋亡增加。 结论：这些新型吡啶嗪酮衍生物有望成为脑癌和肝癌化疗的新候选药物。

  DOI：

  10.2174/1570178614666170707154210

文献信息

• Synthesis and analgesic and anti-inflammatory activities 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substituted/nonsubstituted benzal)hydrazone derivatives
  作者：Mehtap Gökçe、Semra Utku、Esra Küpeli

  DOI：10.1016/j.ejmech.2009.04.048

  日期：2009.9

  this study new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substituted benzal)hydrazone V derivatives were synthesized as analgesic and anti-inflammatory agents. The structures of compounds were elucidated by spectral and elemental analysis. Compounds Va, Vb and Vc were exhibited more potent analgesic activity than ASA. Also these derivatives demonstrated anti-inflammatory activity as well as standard

  在该研究中，合成了新的6-取代的3（2 H）-哒嗪酮-2-乙酰基-2-（对位的取代苯并））Ⅴ衍生物作为镇痛药和消炎药。通过光谱和元素分析阐明了化合物的结构。化合物Va，Vb和Vc比ASA具有更强的镇痛作用。这些衍生物以及标准化合物消炎痛也显示出抗炎活性。检查了这些化合物对胃粘膜的副作用。与参考非甾体类抗炎药（NSAIDs）相比，这些化合物均未显示出胃溃疡作用。在现有数据的基础上，还讨论了V衍生物的结构-活性关系。
• The Novel Synthesized Pyridazinone Derivates had the Antiproliferative and Apoptotic Effects in SHSY5Y and HEP3B Cancer Cell Line
  作者：Osman Ciftci、Zeynep Ozdemir、Ceren Acar、Mert Sozen、Nese Basak-Turkmen、Idris Ayhan、Harika Gozukara

  DOI：10.2174/1570178614666170707154210

  日期：2018.3.9

  Background: Brain cancer (neuroblastoma) and liver cancer (hepatocellular carcinoma) are common cancer types among others worldwide which do not have a radical treatment and cure. Objective: In the current study, five novel pyridazinone derivates bearing benzelhydrazone moiety at second position were synthesized and evaluated for their cytotoxic activity against neuroblastoma and hepatocellular carcinoma (SHSY5Y and HEP3B) and human fibroblast (HF) cell lines. The aim of the current study is to identify antiproliferative activity of five novel pyridazinone derivates against neuroblastoma and hepatocellular carcinoma (SHSY5Y and HEP3B) and human fibroblast (HF) cell lines. Method: The compounds were synthesized by the reacting 6-[4-(phenyl/4-chlorophenyl)piperazine-1- yl]-3(2H)-pyridazinone-2-yl acetohydrazide with benzaldehyde in ethanol. The in vitro antiproliferative activities were determined with MTT assay. Bax, Bcl-2 and Casp3 gene expression levels were detected with RT-PCR analyses. Results: The lowest IC50 was observed for compound 4 in SHSY5Y and HEP3B cells. Apoptosis increased in cancer cells which was shown by changes inBax, Bcl-2 and Casp3 gene expression levels with 1-5 compound therapy. Conclusion: Novel pyridazinone derivates might be promising agents as new chemotherapeutic candidates in brain and liver cancer.

  这是一篇关于研究新型吡啶嗪酮衍生物抗癌活性的论文摘要,我将其翻译如下: 背景：脑癌(神经母细胞瘤)和肝癌(肝细胞癌)是全球常见的癌症类型,目前尚无根治性治疗方法。 目标：本研究合成了5种在2位含有苯甲酰肼基团的新型吡啶嗪酮衍生物,并评估了它们对神经母细胞瘤、肝细胞癌(SHSY5Y和HEP3B)和人成纤维细胞(HF)细胞系的细胞毒性活性。本研究旨在确定这5种新型吡啶嗪酮衍生物对上述细胞系的抗增殖活性。 方法：通过6-[4-(苯基/4-氯苯基)哌嗪-1-基]-3(2H)-吡啶嗪酮-2-基乙酰肼与苯甲醛在乙醇中反应合成目标化合物。采用MTT法测定体外抗增殖活性。通过RT-PCR分析检测Bax、Bcl-2和Casp3基因表达水平。 结果：化合物4在SHSY5Y和HEP3B细胞中显示出最低的IC50值。1-5号化合物治疗导致癌细胞中Bax、Bcl-2和Casp3基因表达水平发生变化,表明细胞凋亡增加。 结论：这些新型吡啶嗪酮衍生物有望成为脑癌和肝癌化疗的新候选药物。
• Synthesis of antipyrine/pyridazinone hybrids and investigation of their in vivo analgesic and anti-inflammatory activities
  作者：SULTAN BAYTAŞ、NAZAN İNCELER、KHATEREH FATTAHPOUR MAVANEH、MECİT ORHAN ULUDAĞ、NURETTİN ABACIOĞLU、MEHTAP GÖKÇE

  DOI：10.3906/kim-1111-29

  日期：——

  Eleven antipyrine/pyridazinone hybrids were synthesized and evaluated for their in vivo analgesic and anti-inflammatory activities by p-benzoquinone-induced writhing test and carrageenan-induced paw edema model, respectively. The test results indicated that compounds 6a, 6c, and 6d were equally or more potent analgesic and anti-inflammatory agents than aspirin and indomethacin, respectively. Side effects of the compounds were examined on gastric mucosa. Most of the compounds were found to be non-ulcerogenic under test conditions.

  合成了 11 种抗吡啶/哒嗪酮杂交化合物，并分别通过对苯醌诱导的蠕动试验和卡拉胶诱导的爪水肿模型对其体内镇痛和抗炎活性进行了评估。 试验结果表明，与阿司匹林和吲哚美辛相比，化合物 6a、6c 和 6d 分别具有相同或更强的镇痛和抗炎作用。研究还考察了化合物对胃黏膜的副作用。 在测试条件下，发现大多数化合物都不会引起溃疡。
• Synthesis and in vitro antimycobacterial activities of novel 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/ nonsubstituted acetophenone) hydrazone
  作者：SEMRA UTKU、MEHTAP GÖKÇE、GÖNÜL ASLAN、GÜL BAYRAM、MAHMUT ÜLGER、GÜROL EMEKDAŞ、MUSTAFA FETHİ ŞAHİN

  DOI：10.3906/kim-1009-63

  日期：——

  The difficulty in managing tuberculosis includes the prolonged duration of the treatment, the emergence of drug resistance, and coinfection with HIV/AIDS. Tuberculosis control requires new drugs that act on novel drug targets to help in combating resistant forms of Mycobacterium tuberculosis and reduce the treatment duration. For this purpose, 6-substituted-3(2H)-pyridazinone-2-acetyl-2- (substituted/nonsubstituted acetophenone) hydrazone derivatives were synthesized and their structures were elucidated by elemental analyses, IR, and ^1H-NMR. The in vitro antimycobacterial activities of synthesized compounds 5a-l were determined by the agar proportion method against Mycobacterium tuberculosis H37Rv. Among the target compounds, 5b and 5f exhibited the best antimycobacterial activity, with a MIC value of 5 \mu g/mL.

  治疗结核病的困难包括治疗时间过长、抗药性的出现以及合并感染艾滋病毒/艾滋病。结核病的控制需要作用于新型药物靶点的新药，以帮助对抗耐药结核分枝杆菌并缩短治疗时间。 为此，我们合成了 6-取代-3(2H)-哒嗪酮-2-乙酰基-2-（取代/未取代苯乙酮）腙衍生物，并通过元素分析、红外光谱和^1H-NMR 阐明了它们的结构。通过琼脂比例法测定了合成化合物 5a-l 对结核分枝杆菌 H37Rv 的体外抗霉活性。 在目标化合物中，5b 和 5f 表现出最好的抗结核活性，其 MIC 值为 5 \mu g/mL。
• 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：——