N-(1-benzylpiperidin-4-yl)-1-(2,3-dimethoxyphenyl)methanimine

• 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-(1-benzylpiperidin-4-yl)-1-(2,3-dimethoxyphenyl)methanimine
• 英文别名: SEW06622
• 化学式: C₂₁H₂₆N₂O₂
• 分子量: 338.45
• InChiKey: GGLDJGOCUBPSEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(1-benzylpiperidin-4-yl)-1-(2,3-dimethoxyphenyl)methanimine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以79%的产率得到1-benzyl-N-(2,3-dimethoxybenzyl)piperidin-4-amine
  参考文献：
  名称：

  Design and development of multitarget-directed N-Benzylpiperidine analogs as potential candidates for the treatment of Alzheimer's disease

  摘要：

  The multitarget-directed strategy offers an effective and promising paradigm to treat the complex neurodegenerative disorder, such as Alzheimer's disease (AD). Herein, a series of N-benzylpiperidine analogs (17-31 and 32-46) were designed and synthesized as multi-functional inhibitors of acetyl cholinesterase (AChE) and beta-secretase-1 (BACE-1) with moderate to excellent inhibitory activities. Among the tested inhibitors, 25, 26, 40, and 41 presented the most significant and balanced inhibition against both the targets. Compounds 40 and 41 exhibited high brain permeability in the PAMPA-BBB assay, significant displacement of propidium iodide from the peripheral anionic site (PAS) of AChE, and were devoid of neurotoxicity towards SH-SY5Y neuroblastoma cell lines up to the maximum tested concentration of 80 mu M. Meanwhile, both these compounds inhibited self- and AChE-induced A beta aggregation in thioflavin T assay, which was also re-affirmed by morphological characterization of All aggregates using atomic force microscopy (AFM). Moreover, 40 and 41 ameliorated the scopolamine induced cognitive impairment in elevated plus and Y-maze experiments. Ex vivo and biochemical analysis established the brain AChE inhibitory potential and antioxidant properties of these compounds. Further, improvement in A beta(1-42)-induced cognitive impairment was also observed by compound 41 in the Morris water maze experiment with significant oral absorption characteristics ascertained by the pharmacokinetic studies. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.030
• 作为产物：
  描述：

  4-氨基-1-苄基哌啶 、 2,3-二甲氧基苯甲醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以93%的产率得到N-(1-benzylpiperidin-4-yl)-1-(2,3-dimethoxyphenyl)methanimine
  参考文献：
  名称：

  Design and development of multitarget-directed N-Benzylpiperidine analogs as potential candidates for the treatment of Alzheimer's disease

  摘要：

  The multitarget-directed strategy offers an effective and promising paradigm to treat the complex neurodegenerative disorder, such as Alzheimer's disease (AD). Herein, a series of N-benzylpiperidine analogs (17-31 and 32-46) were designed and synthesized as multi-functional inhibitors of acetyl cholinesterase (AChE) and beta-secretase-1 (BACE-1) with moderate to excellent inhibitory activities. Among the tested inhibitors, 25, 26, 40, and 41 presented the most significant and balanced inhibition against both the targets. Compounds 40 and 41 exhibited high brain permeability in the PAMPA-BBB assay, significant displacement of propidium iodide from the peripheral anionic site (PAS) of AChE, and were devoid of neurotoxicity towards SH-SY5Y neuroblastoma cell lines up to the maximum tested concentration of 80 mu M. Meanwhile, both these compounds inhibited self- and AChE-induced A beta aggregation in thioflavin T assay, which was also re-affirmed by morphological characterization of All aggregates using atomic force microscopy (AFM). Moreover, 40 and 41 ameliorated the scopolamine induced cognitive impairment in elevated plus and Y-maze experiments. Ex vivo and biochemical analysis established the brain AChE inhibitory potential and antioxidant properties of these compounds. Further, improvement in A beta(1-42)-induced cognitive impairment was also observed by compound 41 in the Morris water maze experiment with significant oral absorption characteristics ascertained by the pharmacokinetic studies. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.030

文献信息

• Design and development of multitarget-directed N-Benzylpiperidine analogs as potential candidates for the treatment of Alzheimer's disease
  作者：Piyoosh Sharma、Avanish Tripathi、Prabhash Nath Tripathi、Santosh Kumar Prajapati、Ankit Seth、Manish Kumar Tripathi、Pavan Srivastava、Vinod Tiwari、Sairam Krishnamurthy、Sushant Kumar Shrivastava

  DOI：10.1016/j.ejmech.2019.02.030

  日期：2019.4

  The multitarget-directed strategy offers an effective and promising paradigm to treat the complex neurodegenerative disorder, such as Alzheimer's disease (AD). Herein, a series of N-benzylpiperidine analogs (17-31 and 32-46) were designed and synthesized as multi-functional inhibitors of acetyl cholinesterase (AChE) and beta-secretase-1 (BACE-1) with moderate to excellent inhibitory activities. Among the tested inhibitors, 25, 26, 40, and 41 presented the most significant and balanced inhibition against both the targets. Compounds 40 and 41 exhibited high brain permeability in the PAMPA-BBB assay, significant displacement of propidium iodide from the peripheral anionic site (PAS) of AChE, and were devoid of neurotoxicity towards SH-SY5Y neuroblastoma cell lines up to the maximum tested concentration of 80 mu M. Meanwhile, both these compounds inhibited self- and AChE-induced A beta aggregation in thioflavin T assay, which was also re-affirmed by morphological characterization of All aggregates using atomic force microscopy (AFM). Moreover, 40 and 41 ameliorated the scopolamine induced cognitive impairment in elevated plus and Y-maze experiments. Ex vivo and biochemical analysis established the brain AChE inhibitory potential and antioxidant properties of these compounds. Further, improvement in A beta(1-42)-induced cognitive impairment was also observed by compound 41 in the Morris water maze experiment with significant oral absorption characteristics ascertained by the pharmacokinetic studies. (C) 2019 Elsevier Masson SAS. All rights reserved.