1-(8-(3-methoxyphenyl)octyl)pyrrolidin-3-ol dimethylcarbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(8-(3-methoxyphenyl)octyl)pyrrolidin-3-ol dimethylcarbamate
• 英文别名: [1-[8-(3-methoxyphenyl)octyl]pyrrolidin-3-yl] N,N-dimethylcarbamate
• 化学式: C₂₂H₃₆N₂O₃
• 分子量: 376.539
• InChiKey: FGPAGOKEVAXSBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  8-(3-methoxyphenyl)octyl bromide 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 24.53h， 生成 1-(8-(3-methoxyphenyl)octyl)pyrrolidin-3-ol dimethylcarbamate
  参考文献：
  名称：

  Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease

  摘要：

  Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our previous studies on cardanol derivatives as acetylcholinesterase (AChE) inhibitors, we designed a novel series of analogues by including a protonable amino moiety belonging to different systems. Properly addressed docking studies suggested that the proposed structural modifications would allow the new molecules to interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, thus being able to act as dual binding inhibitors. To disclose whether the new molecules showed the desired profile, they were first tested for their cholinesterase inhibitory activity towards EeAChE and eqBuChE. Compound 26, bearing an N-ethyl-N-(2-methoxybenzyl)amine moiety, showed the highest inhibitory activity against EeAChE, with a promising IC50 of 6.6 mu M, and a similar inhibition profile of the human isoform (IC50 = 5.7 mu M). As another positive feature, most of the derivatives did not show appreciable toxicity against HT-29 cells, up to a concentration of 100 mu M, which indicates drug conform behavior. Also, compound 26 is capable of crossing the blood brain barrier (BBB), as predicted by a PAMPA-BBB assay. Collectively, the data suggest that the approach to obtain potential anti Alzheimer drugs from CNSL is worth of further pursuit and development. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.024

文献信息

• Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease
  作者：Laís Flávia Nunes Lemes、Giselle de Andrade Ramos、Andressa Souza de Oliveira、Fernanda Motta R. da Silva、Gina de Castro Couto、Marina da Silva Boni、Marcos Jorge R. Guimarães、Isis Nem O. Souza、Manuela Bartolini、Vincenza Andrisano、Patrícia Coelho do Nascimento Nogueira、Edilberto Rocha Silveira、Guilherme D. Brand、Ondřej Soukup、Jan Korábečný、Nelilma C. Romeiro、Newton G. Castro、Maria Laura Bolognesi、Luiz Antonio Soares Romeiro

  DOI：10.1016/j.ejmech.2015.12.024

  日期：2016.1

  Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our previous studies on cardanol derivatives as acetylcholinesterase (AChE) inhibitors, we designed a novel series of analogues by including a protonable amino moiety belonging to different systems. Properly addressed docking studies suggested that the proposed structural modifications would allow the new molecules to interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, thus being able to act as dual binding inhibitors. To disclose whether the new molecules showed the desired profile, they were first tested for their cholinesterase inhibitory activity towards EeAChE and eqBuChE. Compound 26, bearing an N-ethyl-N-(2-methoxybenzyl)amine moiety, showed the highest inhibitory activity against EeAChE, with a promising IC50 of 6.6 mu M, and a similar inhibition profile of the human isoform (IC50 = 5.7 mu M). As another positive feature, most of the derivatives did not show appreciable toxicity against HT-29 cells, up to a concentration of 100 mu M, which indicates drug conform behavior. Also, compound 26 is capable of crossing the blood brain barrier (BBB), as predicted by a PAMPA-BBB assay. Collectively, the data suggest that the approach to obtain potential anti Alzheimer drugs from CNSL is worth of further pursuit and development. (C) 2015 Elsevier Masson SAS. All rights reserved.