N¹,N⁶-bis(6-chloro-1,2,3,4-tetrahydroacridine-9-yl)hexan-1,6-diamine

• 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: N¹,N⁶-bis(6-chloro-1,2,3,4-tetrahydroacridine-9-yl)hexan-1,6-diamine
• 英文别名: N,N'-bis(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)-1,6-hexanediamine；6-chloro-N-{6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl}-1,2,3,4-tetrahydroacridin-9-amine；N,N'-bis(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)hexane-1,6-diamine
• 化学式: C₃₂H₃₆Cl₂N₄
• 分子量: 547.571
• InChiKey: IXRJZUFMXJZPOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N¹,N⁶-bis(6-chloro-1,2,3,4-tetrahydroacridine-9-yl)hexan-1,6-diamine 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 N,N'-bis(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)-1,6-hexanediamine dihydrochloride
  参考文献：
  名称：

  Pyrano[3,2-c]quinoline−6-Chlorotacrine Hybrids as a Novel Family of Acetylcholinesterase- and β-Amyloid-Directed Anti-Alzheimer Compounds

  摘要：

  Two isomeric series of dual binding site acetyleholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase, AChE-induced and self-induced beta-amyloid (A beta) aggregation, and beta-secretase (BACE-1) and to cross blood-brain barrier. The new hybrids consist of a unit of 6-chlorotacrine and a multicomponent reaction-derived pyrano[3,2-c]-quinoline scaffold as the active-site and peripheral-site interacting moieties, respectively, connected through an oligomethylene linker containing an amido group at variable position. Indeed, molecular modeling and kinetic studies have confirmed the dual site binding of these compounds. The new hybrids, and particularly 27, retain the potent and selective human AChE inhibitory activity of the parent 6-chlorotacrine while exhibiting a significant in vitro inhibitory activity toward the AChE-induced and self-induced A beta aggregation and toward BACE-1, as well as ability to enter the central nervous system, which makes them promising anti-Alzheimer lead compounds.

  DOI：

  10.1021/jm900859q
• 作为产物：
  描述：

  2-氨基-4-氯苯甲酸 在 sodium iodide 、 三氯氧磷 、 苯酚 作用下， 反应 4.0h， 生成 N¹,N⁶-bis(6-chloro-1,2,3,4-tetrahydroacridine-9-yl)hexan-1,6-diamine
  参考文献：
  名称：

  同二聚他克林同类物是乙酰胆碱酯酶抑制剂。

  摘要：

  在寻找他克林（1a）的高选择性和有效衍生物的过程中，合成了许多同二聚他克林同源物，并研究了它们对大鼠乙酰胆碱酯酶（AChE）和人丁酰胆碱酯酶（BChE）的抑制作用。发现庚烯连接的双-（6-氯）他克林（3h）抑制大鼠AChE的效力分别比他克林和未取代的双-他克林3b高3000倍和3倍。与3b相比，二聚他克林碳环的大小变化降低了AChE抑制的选择性和效力。将氮杂作为所需的等位基因3j-m插入他克林核中会产生中等效力，但往往对选择性有害。通过在同源二聚啶的6-位掺入卤素，可以显着提高AChE抑制能力和AChE / BChE选择性。3a-m的测定结果也提供了证据，表明7-亚甲基系链倾向于AChE抑制能力最佳。

  DOI：

  10.1021/jm010308g

文献信息

• Bistacrine derivatives as new potent antimalarials
  作者：Ines Schmidt、Gabriele Pradel、Ludmilla Sologub、Alexandra Golzmann、Che J. Ngwa、Anna Kucharski、Tanja Schirmeister、Ulrike Holzgrabe

  DOI：10.1016/j.bmc.2016.06.003

  日期：2016.8

  Linking two tacrine molecules results in a tremendous increase of activity against Plasmodia in comparison to the monomer. This finding prompted the synthesis of a library of monomeric and dimeric tacrine derivatives in order to derive structure–activity relationships. The most active compounds towards chloroquine sensitive Plasmodium strain 3D7 and chloroquine resistant strain Dd2 show IC50 values

  与单体相比，连接两个他克林分子导致抗疟原虫的活性大大增加。这一发现促进了单体和二聚他克林衍生物库的合成，以推导结构-活性关系。对氯喹敏感的疟原虫菌株3D7和对氯喹耐药的菌株Dd2最具活性的化合物在纳摩尔浓度范围内显示IC 50值，细胞毒性低，并靶向半胱氨酸蛋白酶falcipain-2，这对寄生虫的生长至关重要。
• A facile synthesis of bis-tacrine isosteres
  作者：Ming-Kuan Hu、Chih-Feng Lu

  DOI：10.1016/s0040-4039(00)00036-8

  日期：2000.3

  An efficient synthesis of highly potent and selective acetylcholinesterase (AChE) inhibitors, bis-tacrines and their isosteres 2-4, has been accomplished by bis-amination of 9-chloro-tetrahydroacridine (9a) and its analogs. The critical intermediates were concisely prepared in situ by heating the corresponding ortho-amino aromatic acids and cycloketones in the presence of phosphorus oxychloride. (C) 2000 Elsevier Science Ltd. All rights reserved.