8-hydroxy-7-nitro-6-(4-methoxyphenyl)-3-oxo-2-(p-tolyl)-2,3,5,6-tetrahydro-cinnoline-4-carbonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 8-hydroxy-7-nitro-6-(4-methoxyphenyl)-3-oxo-2-(p-tolyl)-2,3,5,6-tetrahydro-cinnoline-4-carbonitrile
• 英文别名: 8-Hydroxy-7-nitro-6-(4-methoxyphenyl)-3-oxo-2-(p-tolyl)-2,3,5,6-tetrahydrocinnoline-4-carbonitrile；8-hydroxy-6-(4-methoxyphenyl)-2-(4-methylphenyl)-7-nitro-3-oxo-5,6-dihydrocinnoline-4-carbonitrile
• 化学式: C₂₃H₁₈N₄O₅
• 分子量: 430.42
• InChiKey: DYEBRSIJICNRPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(4-甲氧苯基)-2-硝基乙烯 、 ethyl 1-p-tolyl-6-oxo-5-cyano-4-methyl-1,6-dihydropyridazine-3-carboxylate 在 哌啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.33h， 以92%的产率得到8-hydroxy-7-nitro-6-(4-methoxyphenyl)-3-oxo-2-(p-tolyl)-2,3,5,6-tetrahydro-cinnoline-4-carbonitrile
  参考文献：
  名称：

  受控微波辐射下绿色高效合成多官能取代的肉桂酸

  摘要：

  摘要 已经开发了一种方便，简单且有效的多官能取代肉桂酸合成方法，该方法涉及在氰基/二恶烷中使5-氰基-4-甲基-1-甲基-1-芳基-6-氧代-1,6-二氢哒嗪-3-羧酸乙酯与硝基烯烃反应。哌啶在受控微波辐射下。所获得的杂环是一些天然化合物和具有广泛生物活性的许多药物中的特权支架。 图形概要

  DOI：

  10.1007/s11164-017-2944-1

文献信息

• Densely functionalized cinnolines: Controlled microwave-assisted facile one-pot multi-component synthesis and in vitro anticancer activity via apoptosis induction
  作者：Maiiada Hassan Nazmy、Ramadan Ahmed Mekheimer、Mai E. Shoman、Mohamed Abo-Elsebaa、Mohamed Abd-Elmonem、Kamal Usef Sadek

  DOI：10.1016/j.bioorg.2020.103932

  日期：2020.8

  There is an urging continuous need for novel anti-cancer agents due to persistent chemoresistance. Herein, newly synthesized cinnolines are evaluated for their possible anticancer activities and suggested mechanisms. In the current study, a simple and efficient synthesis of densely functionalized cinnolines has been developed that relied on multi-component reaction of ethyl 5-cyano-4-methyl-1-aryl-6-oxo-1,6-dihydropyridazine-3-carbox-ylates with aromatic aldehydes and nitromethane in dioxane/pipridine under controlled microwave heating. Selected cinnolines (4a-c, e, h, j-n, q-v) were tested for possible anticancer activity using in vitro one dose assay at National Cancer institute, USA. Only cinnoline 4b stood out as the most potent cinnoline derivative (mean GI %=26.33) with broad-spectrum antitumor activity against the most tested cancer cell lines from all subpanels. The target cinnoline 4b emerged as the most active derivative against both leukemia RPMI-8226 and melanoma LOX IMVI cell lines (GI% = 106.06 and 82.1) respectively, with IC50 values equal to 17.12 +/- 1.31 and 12.32 +/- 0.75 mu g/mL, which are comparable to those of staurosporin; 24.97 +/- 1.47 and 8.45 +/- 0.42 mu g/mL, respectively. Cinnoline 4b influenced cell cycle distribution causing pre-G1 apoptosis and cell growth arrest at G2/M phase. It also induced apoptosis in both cell lines as manifested by significant increase in the percent of annexin V-FITC positive apoptotic cells in leukemia RPMI-8226 cells (from 1.09% to 12.47%) and melanoma LOX IMVI (from 1.32% to 19.05%). In addition, it showed lower expression levels of anti-apoptotic Bcl-2 protein, and higher expression levels of pro-apoptotic proteins; Bax, p53, cytochrome c, caspases 3 and 9. Conclusion: Induction of mitochondrial intrinsic pathway of apoptosis is a possible mechanism by which cin-noline 4b may confer its anticancer activity.