N-(8-((6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino)octyl)-7-((3-chloro-6-methyl-5,5-dioxido-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-yl)amino)heptanamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(8-((6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino)octyl)-7-((3-chloro-6-methyl-5,5-dioxido-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-yl)amino)heptanamide
• 英文别名: 7-[(3-chloro-6-methyl-5,5-dioxo-11H-benzo[c][2,1]benzothiazepin-11-yl)amino]-N-[8-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]octyl]heptanamide
• 化学式: C₄₂H₅₃Cl₂N₅O₃S
• 分子量: 778.887
• InChiKey: WVGUEYXUJOQRDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.6
• 重原子数：
  53
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-chloro-9-(8-aminooctylamino)-1,2,3,4-tetrahydroacridine 、 噻奈普汀 在 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 二氯甲烷 为溶剂， 反应 22.0h， 以70%的产率得到N-(8-((6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino)octyl)-7-((3-chloro-6-methyl-5,5-dioxido-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-yl)amino)heptanamide
  参考文献：
  名称：

  Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S100B secretion and a molecular modeling approach

  摘要：

  Tianeptine was linked to various 9-aminoalkylamino-1,2,3,4-tetrahydroacridines using EDC center dot HCl/HOBt to afford a series of tacrine-tianeptine hybrids. The hybrids were tested for their ability to inhibit AChE and BuChE and IC50 values in the nanomolar concentration scale were obtained. AChE molecular modeling studies of these hybrids indicated that tacrine moiety interacts in the bottom of the gorge with the catalytic active site (CAS) while tianeptine binds to peripheral anionic site (PAS).Furthermore, the compounds 2g and 2e were able to reduce the in vitro basal secretion of S100B, suggesting its therapeutic action in some cases or stages of Alzheimer's disease. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.06.025

文献信息

• Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S100B secretion and a molecular modeling approach
  作者：Marco Antonio Ceschi、Jessie Sobieski da Costa、João Paulo Bizarro Lopes、Viktor Saraiva Câmara、Leandra Franciscato Campo、Antonio César de Amorim Borges、Carlos Alberto Saraiva Gonçalves、Daniela Fraga de Souza、Eduardo Luis Konrath、Ana Luiza Martins Karl、Isabella Alvim Guedes、Laurent Emmanuel Dardenne

  DOI：10.1016/j.ejmech.2016.06.025

  日期：2016.10

  Tianeptine was linked to various 9-aminoalkylamino-1,2,3,4-tetrahydroacridines using EDC center dot HCl/HOBt to afford a series of tacrine-tianeptine hybrids. The hybrids were tested for their ability to inhibit AChE and BuChE and IC50 values in the nanomolar concentration scale were obtained. AChE molecular modeling studies of these hybrids indicated that tacrine moiety interacts in the bottom of the gorge with the catalytic active site (CAS) while tianeptine binds to peripheral anionic site (PAS).Furthermore, the compounds 2g and 2e were able to reduce the in vitro basal secretion of S100B, suggesting its therapeutic action in some cases or stages of Alzheimer's disease. (C) 2016 Elsevier Masson SAS. All rights reserved.