N-(2-(1-benzylpiperidin-4-yl)ethyl)-8-hydroxy-4-oxo-1,4-dihydroquinoline-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-(2-(1-benzylpiperidin-4-yl)ethyl)-8-hydroxy-4-oxo-1,4-dihydroquinoline-2-carboxamide
• 英文别名: N-[2-(1-benzylpiperidin-4-yl)ethyl]-8-hydroxy-4-oxo-1H-quinoline-2-carboxamide
• 化学式: C₂₄H₂₇N₃O₃
• 分子量: 405.497
• InChiKey: AZLXAYYWUXDYQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  81.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  dimethyl 2-((2-methoxyphenyl)amino)but-2-enedioate 在 三甲基铝 、 三溴化硼 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.28h， 生成 N-(2-(1-benzylpiperidin-4-yl)ethyl)-8-hydroxy-4-oxo-1,4-dihydroquinoline-2-carboxamide
  参考文献：
  名称：

  Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease

  摘要：

  In this work we describe neurogenic and neuroprotective donepezil-flavonoid hybrids (DFHs), exhibiting nanomolar affinities for the sigma-1 receptor (sigma R-1) and inhibition of key enzymes in Alzheimer's disease (AD), such as acetylcholinesterase (AChE), 5-lipoxygenase (5-LOX), and monoamine oxidases (MAOs). In general, new compounds scavenge free radical species, are predicted to be brain-permeable, and protect neuronal cells against mitochondrial oxidative stress. N-(2-(1-Benzylpiperidin-4-yl)ethyl)-6,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide (18) is highlighted due to its interesting biological profile in sigma R-1, AChE, 5-LOX, MAO-A and MAO-B. In phenotypic assays, it protects a neuronal cell line against mitochondrial oxidative stress and promotes maturation of neural stem cells into a neuronal phenotype, which could contribute to the reparation of neuronal tissues. Molecular modelling studies of 18 in AChE, 5-LOX and sigma R-1 revealed the main interactions with these proteins, which will be further exploited in the optimization of new, more efficient DFHs. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.07.026

文献信息

• Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease
  作者：Martín Estrada Valencia、Clara Herrera-Arozamena、Lucía de Andrés、Concepción Pérez、José A. Morales-García、Ana Pérez-Castillo、Eva Ramos、Alejandro Romero、Dolores Viña、Matilde Yáñez、Erik Laurini、Sabrina Pricl、María Isabel Rodríguez-Franco

  DOI：10.1016/j.ejmech.2018.07.026

  日期：2018.8

  In this work we describe neurogenic and neuroprotective donepezil-flavonoid hybrids (DFHs), exhibiting nanomolar affinities for the sigma-1 receptor (sigma R-1) and inhibition of key enzymes in Alzheimer's disease (AD), such as acetylcholinesterase (AChE), 5-lipoxygenase (5-LOX), and monoamine oxidases (MAOs). In general, new compounds scavenge free radical species, are predicted to be brain-permeable, and protect neuronal cells against mitochondrial oxidative stress. N-(2-(1-Benzylpiperidin-4-yl)ethyl)-6,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide (18) is highlighted due to its interesting biological profile in sigma R-1, AChE, 5-LOX, MAO-A and MAO-B. In phenotypic assays, it protects a neuronal cell line against mitochondrial oxidative stress and promotes maturation of neural stem cells into a neuronal phenotype, which could contribute to the reparation of neuronal tissues. Molecular modelling studies of 18 in AChE, 5-LOX and sigma R-1 revealed the main interactions with these proteins, which will be further exploited in the optimization of new, more efficient DFHs. (C) 2018 Elsevier Masson SAS. All rights reserved.