N¹-ethyl-N4-(1,2,3,4-tetrahydroacridin-9-yl)butane-1,4-diamine | 1359984-11-4

• 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-ethyl-N4-(1,2,3,4-tetrahydroacridin-9-yl)butane-1,4-diamine
• 英文别名: N-ethyl-N'-(1,2,3,4-tetrahydroacridin-9-yl)butane-1,4-diamine
• CAS: 1359984-11-4
• 化学式: C₁₉H₂₇N₃
• 分子量: 297.443
• InChiKey: YOZFABKPLAMYDE-UHFFFAOYSA-N

物化性质

• 沸点：
  493.4±45.0 °C(Predicted)
• 密度：
  1.083±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯-N-[4-(4-甲氧基苯基)-噻唑-2-基]-乙酰胺 、 N¹-ethyl-N4-(1,2,3,4-tetrahydroacridin-9-yl)butane-1,4-diamine 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以43%的产率得到2-(ethyl(4-(1,2,3,4-tetrahydroacridin-9-ylamino)butyl)amino)-N-(4-(4-methoxyphenyl)thiazol-2-yl)acetamide
  参考文献：
  名称：

  Novel multipotent phenylthiazole–tacrine hybrids for the inhibition of cholinesterase activity, β-amyloid aggregation and Ca2+ overload

  摘要：

  In this study, a series of multipotent phenylthiazole-tacrine hybrids (7a-7e, 8, and 9a-9m) were synthesized and biologically evaluated. Screening results showed that phenylthiazole-tacrine hybrids were potent cholinesterase inhibitors with pIC(50) (-logIC(50)) value ranging from 5.78 +/- 0.05 to 7.14 +/- 0.01 for acetylcholinesterase (AChE), and from 5.75 +/- 0.03 to 10.35 +/- 0.15 for butyrylcholinesterase (BuChE). The second series of phenylthiazole-tacrine hybrids (9a-9m) could efficiently prevent A beta(1-42) self-aggregation. The structure-activity relationship revealed that their inhibitory potency relied on the type of middle linker and substitutions at 4'-position of 4-phenyl-2-aminothiazole. In addition, 7a and 7c also displayed the Ca2+ overload blockade effect in the primary cultured cortical neurons. Consequently, these compounds emerged as promising molecules for the therapy of Alzheimer's disease. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.040
• 作为产物：
  描述：

  9-(4-aminobutylamino)-1,2,3,4-tetrahydroacridine 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 48.08h， 生成 N¹-ethyl-N4-(1,2,3,4-tetrahydroacridin-9-yl)butane-1,4-diamine
  参考文献：
  名称：

  CANNABINOID RECEPTOR SUBTYPE 2 STIMULATOR INHIBITING ACETYLCHOLINESTERASE AND BUTYRYLCHOLINESTERASE

  摘要：

  该发明涉及一种化合物，其化学式如下：其中R6为H或烷基，R5和R7中的一个包含或由连接子耦合的他克林残基组成，其中连接子与他克林残基的氨基残基耦合，并将他克林残基与分子的其余部分耦合，R5和R7中的另一个为H或烷基。

  公开号：

  EP3771713A1

文献信息

• Dual-Acting Cholinesterase–Human Cannabinoid Receptor 2 Ligands Show Pronounced Neuroprotection in Vitro and Overadditive and Disease-Modifying Neuroprotective Effects in Vivo
  作者：Matthias Scheiner、Dominik Dolles、Sandra Gunesch、Matthias Hoffmann、Massimo Nabissi、Oliviero Marinelli、Marina Naldi、Manuela Bartolini、Sabrina Petralla、Eleonora Poeta、Barbara Monti、Christina Falkeis、Michael Vieth、Harald Hübner、Peter Gmeiner、Rangan Maitra、Tangui Maurice、Michael Decker

  DOI：10.1021/acs.jmedchem.9b00623

  日期：2019.10.24

  We have designed and synthesized a series of 14 hybrid molecules out of the cholinesterase (ChE) inhibitor tacrine and a benzimidazole-based human cannabinoid receptor subtype 2 (hCB(2)R) agonist and investigated them in vitro and in vivo. The compounds are potent ChE inhibitors, and for the most promising hybrids, the mechanism of human acetylcholinesterase (hAChE) inhibition as well as their ability to interfere with AChE-induced aggregation of beta-amyloid (A beta), and A beta self-aggregation was assessed. All hybrids were evaluated for affinity and selectivity for hCB(1)R and hCB(2)R. To ensure that the hybrids retained their agonist character, the expression of cAMP-regulated genes was quantified, and potency and efficacy were determined. Additionally, the effects of the hybrids on microglia activation and neuroprotection on HT-22 cells were investigated. The most promising in vitro hybrids showed pronounced neuroprotection in an Alzheimer's mouse model at low dosage (0.1 mg/kg, i.p.), lacking hepatotoxicity even at high dose (3 mg/kg, i.p.).