(E)-N-((1-benzylpiperidin-4-yl)methyl)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylamide

• 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: (E)-N-((1-benzylpiperidin-4-yl)methyl)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylamide
• 英文别名: (E)-N-[(1-benzylpiperidin-4-yl)methyl]-3-(3,5-ditert-butyl-4-hydroxyphenyl)prop-2-enamide
• 化学式: C₃₀H₄₂N₂O₂
• 分子量: 462.676
• InChiKey: RCLZNVUFTLOILJ-OUKQBFOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-苄基-4-氰基哌啶 在 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醚 为溶剂， 反应 4.0h， 生成 (E)-N-((1-benzylpiperidin-4-yl)methyl)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylamide
  参考文献：
  名称：

  Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease agents with cholinergic, antioxidant, and neuroprotective properties

  摘要：

  The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC50, 0.075 mu M for eeAChE and 0.75 mu M for hAChE) and Monoamine oxidase B (MAO-B) inhibition (IC50, 7.4 mu M for hMAO-B), excellent antioxidant activity (71.7 mu M of IC50 by DPPH method, 0.82 and 1.62 trolox equivalent by ABTS method and ORAC method respectively), and inhibitory effects on self-induced, hAChE-induced A beta aggregation. Moreover, 7d possessed neuroprotective potency against H2O2-induced oxidative damage on PC12 cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 cells. Compound 7d was capable of penetrating BBB and presented good liver microsomal metabolic stability. Importantly, compound 7d could dose-dependently reverse scopolamine-induced memory deficit in mice without acute toxicity. Taken together, those outstanding results highlight the donepezil-BHT hybrid 7d as a promising prototype in the research of innovative compound for AD. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.08.005

文献信息

• Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease agents with cholinergic, antioxidant, and neuroprotective properties
  作者：Pei Cai、Si-Qiang Fang、Hua-Li Yang、Xue-Lian Yang、Qiao-Hong Liu、Ling-Yi Kong、Xiao-Bing Wang

  DOI：10.1016/j.ejmech.2018.08.005

  日期：2018.9

  The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC50, 0.075 mu M for eeAChE and 0.75 mu M for hAChE) and Monoamine oxidase B (MAO-B) inhibition (IC50, 7.4 mu M for hMAO-B), excellent antioxidant activity (71.7 mu M of IC50 by DPPH method, 0.82 and 1.62 trolox equivalent by ABTS method and ORAC method respectively), and inhibitory effects on self-induced, hAChE-induced A beta aggregation. Moreover, 7d possessed neuroprotective potency against H2O2-induced oxidative damage on PC12 cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 cells. Compound 7d was capable of penetrating BBB and presented good liver microsomal metabolic stability. Importantly, compound 7d could dose-dependently reverse scopolamine-induced memory deficit in mice without acute toxicity. Taken together, those outstanding results highlight the donepezil-BHT hybrid 7d as a promising prototype in the research of innovative compound for AD. (C) 2018 Elsevier Masson SAS. All rights reserved.