N-(6-selenocyanatohexyl)-N-(1',2',3',4'-tetrahydroacridin-9'-y)lamino

• 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-(6-selenocyanatohexyl)-N-(1',2',3',4'-tetrahydroacridin-9'-y)lamino
• 英文别名: 6-(1,2,3,4-Tetrahydroacridin-9-ylamino)hexyl selenocyanate；6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexyl selenocyanate
• 化学式: C₂₀H₂₅N₃Se
• 分子量: 386.399
• InChiKey: SSDPRLZRABLZQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.69
• 重原子数：
  24
• 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：
  48.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(6-selenocyanatohexyl)-N-(1',2',3',4'-tetrahydroacridin-9'-y)lamino 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以31%的产率得到bis[5-(1',2',3',4'-tetrahydroacridin-9'-ylamino)hexyl]diselenide
  参考文献：
  名称：

  New tacrine dimers with antioxidant linkers as dual drugs: Anti-Alzheimer's and antiproliferative agents

  摘要：

  We have designed a series of tacrine-based homo-and heterodimers that incorporate an antioxidant tether (selenoureido, chalcogenide) as new dual compounds: for the treatment of Alzheimer's disease and as antiproliferative agents. Symmetrical homodimers bearing a dichalcogenide or selenide-based tether, the best compounds in the series, were found to be strong and highly selective electric eel AChE inhibitors, with inhibition constants within the low nanomolar range. This high inhibitory activity was confirmed on recombinant human AChE for the most interesting derivatives. The three most promising homodimers also showed a good inhibitory activity towards amyloid-beta self aggregation. The symmetric disulfide derivative bis[5-(1',2',3',4'-tetrahydroacridin-9'-ylamino)pentyl]clisulfide (19) showed the best multipotent profile and was not neurotoxic on immortalized mouse cortical neurons even at 50 mu M concentration. These results represent an improvement in activity and selectivity compared to parent tacrine, the first marketed drug against Alzheimer's disease.Title compounds also exhibited excellent in vitro antiproliferative activities against a panel of 6 human tumor cell lines, with GI(50) values within the submicromolar range for the most potent derivatives (0.12 -0.95 mu M); such values represent a spectacular increase compared to currently-used chemotherapeutic agents, such as 5-FU (up to 306 fold) and cisplatin (up to 162 fold). Cell cycle experiments indicated the accumulation of cells in the G(1) phase of the cycle, a different mechanism than the reported for cisplatin. The breast cancer cell lines turned out to be the most sensitive one of the panel tested. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.048
• 作为产物：
  描述：

  9-胺-1,2,3,4-四氢盐酸氯酯 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 N-(6-selenocyanatohexyl)-N-(1',2',3',4'-tetrahydroacridin-9'-y)lamino
  参考文献：
  名称：

  New tacrine dimers with antioxidant linkers as dual drugs: Anti-Alzheimer's and antiproliferative agents

  摘要：

  We have designed a series of tacrine-based homo-and heterodimers that incorporate an antioxidant tether (selenoureido, chalcogenide) as new dual compounds: for the treatment of Alzheimer's disease and as antiproliferative agents. Symmetrical homodimers bearing a dichalcogenide or selenide-based tether, the best compounds in the series, were found to be strong and highly selective electric eel AChE inhibitors, with inhibition constants within the low nanomolar range. This high inhibitory activity was confirmed on recombinant human AChE for the most interesting derivatives. The three most promising homodimers also showed a good inhibitory activity towards amyloid-beta self aggregation. The symmetric disulfide derivative bis[5-(1',2',3',4'-tetrahydroacridin-9'-ylamino)pentyl]clisulfide (19) showed the best multipotent profile and was not neurotoxic on immortalized mouse cortical neurons even at 50 mu M concentration. These results represent an improvement in activity and selectivity compared to parent tacrine, the first marketed drug against Alzheimer's disease.Title compounds also exhibited excellent in vitro antiproliferative activities against a panel of 6 human tumor cell lines, with GI(50) values within the submicromolar range for the most potent derivatives (0.12 -0.95 mu M); such values represent a spectacular increase compared to currently-used chemotherapeutic agents, such as 5-FU (up to 306 fold) and cisplatin (up to 162 fold). Cell cycle experiments indicated the accumulation of cells in the G(1) phase of the cycle, a different mechanism than the reported for cisplatin. The breast cancer cell lines turned out to be the most sensitive one of the panel tested. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.048