N-(6-azidohexyl)-1,2,3,4-tetrahydroacridin-9-amine

• 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-azidohexyl)-1,2,3,4-tetrahydroacridin-9-amine
• 化学式: C₁₉H₂₅N₅
• 分子量: 323.441
• InChiKey: DYNUCCKWSCYBBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  39.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(6-azidohexyl)-1,2,3,4-tetrahydroacridin-9-amine 在 palladium on activated charcoal 、 氢气 作用下， 生成 N1-(1,2,3,4-tetrahydroacridin-9-yl)hexane-1,6-diamine
  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 azide 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(6-azidohexyl)-1,2,3,4-tetrahydroacridin-9-amine
  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

文献信息

• Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors
  作者：Quelli Larissa Oliveira de Santana、Tereza C. Santos Evangelista、Petra Imhof、Sabrina Baptista Ferreira、José G. Fernández-Bolaños、Magne O. Sydnes、Óscar Lopéz、Emil Lindbäck

  DOI：10.1039/d0ob02588g

  日期：——

  We have used the Cu(I)-catalyzed azide–alkyne Huisgen cycloaddition reaction to obtain two families of bivalent heterodimers where tacrine is connected to an azasugar or iminosugar, respectively, via linkers of variable length. The heterodimers were investigated as cholinesterase inhibitors and it was found that their activity increased with the length of the linker. Two of the heterodimers were significantly

  我们已经使用Cu（I）催化的叠氮化物-炔烃惠斯根环加成反应获得了两个家族的二价异二聚体，其中他克林分别通过以下途径连接至氮杂糖或亚氨基糖：可变长度的接头。研究了异二聚体作为胆碱酯酶抑制剂，发现它们的活性随连接子长度的增加而增加。两种异二聚体比单体他克林具有更强的乙酰胆碱酯酶抑制剂。分子模型表明，较长的异二聚体比较短的对应物更适合乙酰胆碱酯酶的活性峡谷，前者提供了与催化阴离子结合位点（CAS）和外围阴离子结合位点（PAS）中色氨酸残基更有效的同时相互作用。
• Development of tacrine clusters as positively cooperative systems for the inhibition of acetylcholinesterase
  作者：Tereza Cristina Santos Evangelista、Óscar López、Sabrina Baptista Ferreira、José G. Fernández-Bolaños、Magne O. Sydnes、Emil Lindbäck

  DOI：10.1080/14756366.2021.1954917

  日期：2021.1.1

  The synthesis of four tetra-tacrine clusters where the tacrine binding units are attached to a central scaffold via linkers of variable lengths is described. The multivalent inhibition potencies for the tacrine clusters were investigated for the inhibition of acetylcholinesterase. Two of the tacrine clusters displayed a small but significant multivalent inhibition potency in which the binding affinity of each of the tacrine binding units increased up to 3.2 times when they are connected to the central scaffold.
• Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers
  作者：I. Caroline Vaaland、Óscar López、Adrián Puerta、Miguel X. Fernandes、José M. Padrón、José G. Fernández-Bolaños、Magne O. Sydnes、Emil Lindbäck

  DOI：10.1080/14756366.2022.2150762

  日期：2023.12.31
• New tacrine dimers with antioxidant linkers as dual drugs: Anti-Alzheimer's and antiproliferative agents
  作者：Jesús M. Roldán-Peña、Daniel Alejandre-Ramos、Óscar López、Inés Maya、Irene Lagunes、José M. Padrón、Luis Emiliano Peña-Altamira、Manuela Bartolini、Barbara Monti、Maria L. Bolognesi、José G. Fernández-Bolaños

  DOI：10.1016/j.ejmech.2017.06.048

  日期：2017.9

  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.