methyl 5-nitro-1-(4-nitrobenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 5-nitro-1-(4-nitrobenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate
• 英文别名: Methyl 5-nitro-1-[(4-nitrophenyl)methyl]-2-oxoquinoline-3-carboxylate；methyl 5-nitro-1-[(4-nitrophenyl)methyl]-2-oxoquinoline-3-carboxylate
• 化学式: C₁₈H₁₃N₃O₇
• 分子量: 383.317
• InChiKey: HSBFQLZMOGSGOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  138
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 5-nitro-1-(4-nitrobenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate 在 N,N-二异丙基乙胺 、 tin(ll) chloride 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.25h， 生成 methyl 5-(adamantane-2-carboxamido)-1-(4-nitrobenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  胶质母细胞瘤细胞中喹啉酮和喹啉基P2X7受体拮抗剂的合成，构效关系及其抗球形成活性

  摘要：

  筛选喹啉酮衍生物的化合物文库，将化合物11a鉴定为新的P2X7受体拮抗剂。为了优化其活性，我们评估了喹啉酮支架在三个不同位置R 1，R 2和R 3的构效关系（SAR）。SAR分析表明，在将R羧酸乙酯基1位置，在r金刚羧酰胺基2和基团R a 4-甲氧基取代3位置是对抗P2X7R活性的最佳取代基。但是，由于大多数喹啉酮衍生物在IL-1βELISA分析中显示出较低的抑制作用，因此核心结构被进一步修饰为带有氯或取代苯基的喹啉骨架。使用喹啉骨架的优化拮抗剂包括2-氯-5-金刚烷基-喹啉衍生物（16c）和2-（4-羟甲基苯基）-5-金刚烷基-喹啉衍生物（17k），IC 50值为4和3 nM，分别。与喹啉酮衍生物相反，喹啉化合物的拮抗作用（16c和17k）与它们抑制促炎细胞因子IL-1β从LPS /IFN-γ/ BzATP刺激的THP-1细胞释放的能力相对应（IC 50分别为7和12 nM）。此外，有效

  DOI：

  10.1016/j.ejmech.2018.03.023
• 作为产物：
  描述：

  methyl 5-nitro-2-oxo-1,2-dihydroquinoline-3-carboxylate 、 对硝基溴化苄 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以40%的产率得到methyl 5-nitro-1-(4-nitrobenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Discovery and structure–activity relationship studies of quinolinone derivatives as potent IL-2 suppressive agents

  摘要：

  The quinolinone skeleton has been utilized to develop various mechanism-based immune modulators. However, the effects of quinolinone derivatives on the release of T cell-associated interleukin-2 (IL-2) have not been established. In this study, a series of novel quinolinone derivatives was synthesized, and their immunosuppressive activity was evaluated by measuring suppression of IL-2 release from activated Jurkat T cells. Optimizing the three side chains around the quinolinone skeleton revealed the most active compound: 111. This compound exhibits potent inhibitory activity toward IL-2 release in both 12-o-tetradecanoylphorbol-13-acetate (PMA)/A23187 (ionomycin) (IC50 = 80 +/- 10 nM) and anti-CD3/CD28-stimulated Jurkat T cells (83% inhibition at 10 mu M) without cytotoxic effects. Further investigation into the underlying mechanism of 111 indicated the suppression of NF-kappa B and nuclear factor of activated T cells (NFAT) promoter activities in Jurkat T cells. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2016.08.051

文献信息

• Discovery and structure–activity relationship studies of quinolinone derivatives as potent IL-2 suppressive agents
  作者：Seung-Hwa Kwak、Jung-Ah Kang、Minjeong Kim、So-Deok Lee、Jin-Hee Park、Sung-Gyoo Park、Hyojin Ko、Yong-Chul Kim

  DOI：10.1016/j.bmc.2016.08.051

  日期：2016.11

  The quinolinone skeleton has been utilized to develop various mechanism-based immune modulators. However, the effects of quinolinone derivatives on the release of T cell-associated interleukin-2 (IL-2) have not been established. In this study, a series of novel quinolinone derivatives was synthesized, and their immunosuppressive activity was evaluated by measuring suppression of IL-2 release from activated Jurkat T cells. Optimizing the three side chains around the quinolinone skeleton revealed the most active compound: 111. This compound exhibits potent inhibitory activity toward IL-2 release in both 12-o-tetradecanoylphorbol-13-acetate (PMA)/A23187 (ionomycin) (IC50 = 80 +/- 10 nM) and anti-CD3/CD28-stimulated Jurkat T cells (83% inhibition at 10 mu M) without cytotoxic effects. Further investigation into the underlying mechanism of 111 indicated the suppression of NF-kappa B and nuclear factor of activated T cells (NFAT) promoter activities in Jurkat T cells. (C) 2016 Published by Elsevier Ltd.
• Synthesis and structure-activity relationships of quinolinone and quinoline-based P2X7 receptor antagonists and their anti-sphere formation activities in glioblastoma cells
  作者：Seung-Hwa Kwak、Seungheon Shin、Ji-Hyun Lee、Jin-Kyoung Shim、Minjeong Kim、So-Deok Lee、Aram Lee、Jinsu Bae、Jin-Hee Park、Aliaa Abdelrahman、Christa E. Müller、Steve K. Cho、Seok-Gu Kang、Myung Ae Bae、Jung Yoon Yang、Hyojin Ko、William A. Goddard、Yong-Chul Kim

  DOI：10.1016/j.ejmech.2018.03.023

  日期：2018.5

  Screening a compound library of quinolinone derivatives identified compound 11a as a new P2X7 receptor antagonist. To optimize its activity, we assessed structure-activity relationships (SAR) at three different positions, R1, R2 and R3, of the quinolinone scaffold. SAR analysis suggested that a carboxylic acid ethyl ester group at the R1 position, an adamantyl carboxamide group at R2 and a 4-methoxy

  筛选喹啉酮衍生物的化合物文库，将化合物11a鉴定为新的P2X7受体拮抗剂。为了优化其活性，我们评估了喹啉酮支架在三个不同位置R 1，R 2和R 3的构效关系（SAR）。SAR分析表明，在将R羧酸乙酯基1位置，在r金刚羧酰胺基2和基团R a 4-甲氧基取代3位置是对抗P2X7R活性的最佳取代基。但是，由于大多数喹啉酮衍生物在IL-1βELISA分析中显示出较低的抑制作用，因此核心结构被进一步修饰为带有氯或取代苯基的喹啉骨架。使用喹啉骨架的优化拮抗剂包括2-氯-5-金刚烷基-喹啉衍生物（16c）和2-（4-羟甲基苯基）-5-金刚烷基-喹啉衍生物（17k），IC 50值为4和3 nM，分别。与喹啉酮衍生物相反，喹啉化合物的拮抗作用（16c和17k）与它们抑制促炎细胞因子IL-1β从LPS /IFN-γ/ BzATP刺激的THP-1细胞释放的能力相对应（IC 50分别为7和12 nM）。此外，有效