3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl]piperidin-4-yl]benzamide | 1446498-70-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl]piperidin-4-yl]benzamide
• CAS: 1446498-70-9
• 化学式: C₂₂H₂₃N₃O₅
• 分子量: 409.442
• InChiKey: VEMVXQOWRPHQDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  126
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-羟基吲哚 在 四丁基氯化铵 、 三溴化硼 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 31.5h， 生成 3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl]piperidin-4-yl]benzamide
  参考文献：
  名称：

  Indole derivatives as dual-effective agents for the treatment of neurodegenerative diseases: Synthesis, biological evaluation, and molecular modeling studies

  摘要：

  Several indole derivatives, that were highly potent ligands of GluN2B-subunit-containing N-methyl-D-aspartate (NMDA) receptor, also demonstrated antioxidant properties in ABTS method. In particular, the 2-(4-benzylpiperidin-1-yl)-1-(5-hydroxy-1H-indol-3-yl)ethanone (1) proved to be a dual-effective neuroprotective agent. With the aim to increase the antioxidant properties we added a catechol moiety onto piperidine moiety. The designed hybrid derivative 3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl]piperidin-4-yl]benzamide (10) was the most effective antioxidant agent (>94.1 +/- 0.1% of inhibition at 17 mu M) and showed GluN2B/NMDA receptor affinity at low micromolar concentration (IC50 0.66 mu M). By means of computational studies we explored the effect of the presence of this antioxidant fragment during the recognition process to binding pocket. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.044

文献信息

• Indole derivatives as dual-effective agents for the treatment of neurodegenerative diseases: Synthesis, biological evaluation, and molecular modeling studies
  作者：Maria Rosa Buemi、Laura De Luca、Alba Chimirri、Stefania Ferro、Rosaria Gitto、Julio Alvarez-Builla、Ramon Alajarin

  DOI：10.1016/j.bmc.2013.05.044

  日期：2013.8

  Several indole derivatives, that were highly potent ligands of GluN2B-subunit-containing N-methyl-D-aspartate (NMDA) receptor, also demonstrated antioxidant properties in ABTS method. In particular, the 2-(4-benzylpiperidin-1-yl)-1-(5-hydroxy-1H-indol-3-yl)ethanone (1) proved to be a dual-effective neuroprotective agent. With the aim to increase the antioxidant properties we added a catechol moiety onto piperidine moiety. The designed hybrid derivative 3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl]piperidin-4-yl]benzamide (10) was the most effective antioxidant agent (>94.1 +/- 0.1% of inhibition at 17 mu M) and showed GluN2B/NMDA receptor affinity at low micromolar concentration (IC50 0.66 mu M). By means of computational studies we explored the effect of the presence of this antioxidant fragment during the recognition process to binding pocket. (C) 2013 Elsevier Ltd. All rights reserved.