3-chloro-6-(4-phenylpiperazin-1-yl)pyridazine

• 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: 3-chloro-6-(4-phenylpiperazin-1-yl)pyridazine
• 化学式: C₁₄H₁₅ClN₄
• mdl: MFCD06757945
• 分子量: 274.753
• InChiKey: QNLZUFZZTZLULV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-chloro-6-(4-phenylpiperazin-1-yl)pyridazine 在 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 6.0h， 生成 ethyl (6-[4-(phenyl)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
• 作为产物：
  描述：

  3,6-二氯哒嗪 、 N-苯基哌嗪 以 乙醇 为溶剂， 反应 6.0h， 生成 3-chloro-6-(4-phenylpiperazin-1-yl)pyridazine
  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 biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents
  作者：Stéphane Sengmany、Mathilde Sitter、Eric Léonel、Erwan Le Gall、Gervaise Loirand、Thierry Martens、Didier Dubreuil、Florian Dilasser、Morgane Rousselle、Vincent Sauzeau、Jacques Lebreton、Muriel Pipelier、Rémy Le Guével

  DOI：10.1016/j.bmcl.2018.12.050

  日期：2019.3

  Various 3-amino-, 3-aryloxy- and alkoxy-6-arylpyridazines have been synthesized by an electrochemical reductive cross-coupling between 3-amino-, 3-aryloxy- or 3-alkoxy-6-chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products was evaluated against a representative panel of cancer cell lines (HuH7, CaCo-2, MDA-MB-231, HCT116, PC3, NCI-H727, HaCaT) and

  通过3-氨基-，3-芳氧基-或3-烷氧基-6-氯哒嗪与芳基或杂芳基卤化物之间的电化学还原交叉偶联，已经合成了各种3-氨基-，3-芳氧基-和烷氧基-6-芳基哒嗪。评估了这些产品对代表性癌细胞系（HuH7，CaCo-2，MDA-MB-231，HCT116，PC3，NCI-H727，HaCaT）的体外抗增殖活性，并强调了更有效衍生物的致癌性预防在建立人类乳腺癌细胞系MDA-MB 468-Luc与p44 / 42和Akt依赖性信号传导途径的相互作用之前，已对MDA-MB 468-Luc进行了研究。
• 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。
• An Electrochemical Nickel-Catalyzed Arylation of 3-Amino-6-Chloropyridazines
  作者：Stéphane Sengmany、Arnaud Vitu-Thiebaud、Erwan Le Gall、Sylvie Condon、Eric Léonel、Christine Thobie-Gautier、Muriel Pipelier、Jacques Lebreton、Didier Dubreuil

  DOI：10.1021/jo3022428

  日期：2013.1.18

  3-Amino-6-aryl- and 3-amino-6-heteroarylpyridazines have been obtained in generally good yield using a nickel-catalyzed electrochemical cross-coupling between 3-amino-6-chloropyridazines and aryl or heteroaryl halides at room temperature. Comparative experiments involving classical palladium-catalyzed reactions, such as Suzuki, Stille, or Negishi cross-couplings, reveal that the electrochemical method can constitute a reliable alternative tool for biaryl formation. A possible reaction mechanism is proposed on the basis of electrochemical analyses.