5-amino-N-(4-hydroxyphenethyl)-1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-3 carboxamide

• 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: 5-amino-N-(4-hydroxyphenethyl)-1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-3 carboxamide
• 英文别名: 5-amino-N-[2-(4-hydroxyphenyl)ethyl]-1-[(4-methoxyphenyl)methyl]-2-oxoquinoline-3-carboxamide
• 化学式: C₂₆H₂₅N₃O₄
• 分子量: 443.502
• InChiKey: QWZQVQHQZHWKTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 1-(4-methoxybenzyl)-5-nitro-2-oxo-1,2-dihydroquinoline-3-carboxylate 在 palladium on activated charcoal 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 5-amino-N-(4-hydroxyphenethyl)-1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-3 carboxamide
  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.