2-(((3-(1-benzylpiperidin-4-yl)propyl)(prop-2-yn-1-yl)amino)methyl)quinolin-8-ol

• 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: 2-(((3-(1-benzylpiperidin-4-yl)propyl)(prop-2-yn-1-yl)amino)methyl)quinolin-8-ol
• 英文别名: 2-[[3-(1-Benzylpiperidin-4-yl)propyl-prop-2-ynylamino]methyl]quinolin-8-ol；2-[[3-(1-benzylpiperidin-4-yl)propyl-prop-2-ynylamino]methyl]quinolin-8-ol
• 化学式: C₂₈H₃₃N₃O
• 分子量: 427.59
• InChiKey: KBSUDEJPIPDJQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  39.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-苄基-4-哌啶甲醛 在 四丁基氟化铵 、 碘 、 二异丁基氢化铝 、 potassium carbonate 、 magnesium 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 31.08h， 生成 2-(((3-(1-benzylpiperidin-4-yl)propyl)(prop-2-yn-1-yl)amino)methyl)quinolin-8-ol
  参考文献：
  名称：

  Donepezil-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation

  摘要：

  Currently available drugs against Alzheimer's disease (AD) are only able to ameliorate the disease symptoms resulting in a moderate improvement in memory and cognitive function without any efficacy in preventing and inhibiting the progression of the pathology. In an effort to obtain disease-modifying anti-Alzheimer's drugs (DMAADs) following the multifactorial nature of AD, we have recently developed multifunctional compounds. We herein describe the design, synthesis, molecular modeling and biological evaluation of a hew series of donepezil-related compounds possessing metal chelating properties, and being capable of targeting different enzymatic systems related to AD (cholinesterases, ChEs, and monoamine oxidase A, MAO-A). Among this set of analogues compound 5f showed excellent ChEs inhibition potency and a selective MAO-A inhibition (vs MAO-B) coupled to strong complexing properties for zinc and copper ions, both known to be involved in the progression of AD. Moreover, 5f exhibited moderate antioxidant properties as found by in vitro assessment. This compound represents a novel donepezil hydroxyquinoline hybrid with DMAAD profile paving the way to the development of a novel class of drugs potentially able to treat AD. (c) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.001

文献信息

• Donepezil-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation
  作者：Ming-Yu Wu、Gerard Esteban、Simone Brogi、Masahi Shionoya、Li Wang、Giuseppe Campiani、Mercedes Unzeta、Tsutomu Inokuchi、Stefania Butini、Jose Marco-Contelles

  DOI：10.1016/j.ejmech.2015.10.001

  日期：2016.10

  Currently available drugs against Alzheimer's disease (AD) are only able to ameliorate the disease symptoms resulting in a moderate improvement in memory and cognitive function without any efficacy in preventing and inhibiting the progression of the pathology. In an effort to obtain disease-modifying anti-Alzheimer's drugs (DMAADs) following the multifactorial nature of AD, we have recently developed multifunctional compounds. We herein describe the design, synthesis, molecular modeling and biological evaluation of a hew series of donepezil-related compounds possessing metal chelating properties, and being capable of targeting different enzymatic systems related to AD (cholinesterases, ChEs, and monoamine oxidase A, MAO-A). Among this set of analogues compound 5f showed excellent ChEs inhibition potency and a selective MAO-A inhibition (vs MAO-B) coupled to strong complexing properties for zinc and copper ions, both known to be involved in the progression of AD. Moreover, 5f exhibited moderate antioxidant properties as found by in vitro assessment. This compound represents a novel donepezil hydroxyquinoline hybrid with DMAAD profile paving the way to the development of a novel class of drugs potentially able to treat AD. (c) 2015 Elsevier Masson SAS. All rights reserved.