6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanoic acid | 873445-17-1

• 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: 6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanoic acid
• CAS: 873445-17-1
• 化学式: C₁₉H₂₄N₂O₂
• 分子量: 312.412
• InChiKey: FHSSNFOPHXCGDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanoic acid 、 4-(2-苯并噻唑基)苯胺 在 4-二甲氨基吡啶 、 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 24.0h， 以40%的产率得到N-(4-(benzo[d]thiazol-2-yl)phenyl)-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide
  参考文献：
  名称：

  Design, synthesis and neuroprotective evaluation of novel tacrine–benzothiazole hybrids as multi-targeted compounds against Alzheimer’s disease

  摘要：

  Alzheimer's disease (AD) is a multifactorial disorder with several target proteins contributing to its etiology. In search for multifunctional anti-AD drug candidates, taking into account that the acetylcholinesterase (AChE) and beta-amyloid (A beta) aggregation are particularly important targets for inhibition, the tacrine and benzothiazole (BTA) moieties were conjugated with suitable linkers in a novel series of hybrids. The designed compounds (7a-7e) were synthesized and in vitro as well as in ex vivo evaluated for their capacity for the inhibition of acetylcholinesterase (AChE) and A beta self-induced aggregation, and also for the protection of neuronal cells death (SHSY-5Y cells, AD and MCI cybrids). All the tacrine-BTA hybrids displayed high in vitro activities, namely with IC50 values in the low micromolar to sub-micromolar concentration range towards the inhibition of AChE, and high percentages of inhibition of the self-induced A beta aggregation. Among them, compound 7a, with the shortest linker, presented the best inhibitory activity of AChE (IC50 = 0.34 mu M), while the highest activity as anti-A beta(42) self-aggregation, was evidenced for compound 7b (61.3%, at 50 mu M. The docking studies demonstrated that all compounds are able to interact with both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Our results show that compounds 7d and 7e improved cell viability in cells treated with A beta(42) peptide. Overall, these multi-targeted hybrid compounds appear as promising lead compounds for the treatment of Alzheimer's disease. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.028
• 作为产物：
  描述：

  6-氨基己酸 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanoic acid
  参考文献：
  名称：

  Novel Tacrine−Melatonin Hybrids as Dual-Acting Drugs for Alzheimer Disease, with Improved Acetylcholinesterase Inhibitory and Antioxidant Properties

  摘要：

  Tacrine and melatonin are well-known drugs with activities as an acetylcholinesterase (AChE) inhibitor and free radical scavenger, respectively. In this work, we report new hybrids of both drugs that display higher in vitro properties than the sum of their parts. As selective inhibitors of human AChE, their IC50 values range from sub-nanomolar to picomolar. They exhibit a higher oxygen radical absorbance capacity than does melatonin and are predicted to be able to cross the blood-brain barrier to reach their targets in the central nervous system.

  DOI：

  10.1021/jm050746d

文献信息

• Tacrine-allyl/propargylcysteine–benzothiazole trihybrids as potential anti-Alzheimer's drug candidates
  作者：Asha Hiremathad、Karam Chand、A. Raquel Esteves、Sandra M. Cardoso、Rona R. Ramsay、Sílvia Chaves、Rangappa S. Keri、M. Amélia Santos

  DOI：10.1039/c6ra03455a

  日期：——

  On continuing our research on new drug candidates for Alzheimer´s disease (AD), we have designed, synthesized and evaluated a series of multifunctional trihybrid agents. The design strategy was based on...

  在继续研究针对阿尔茨海默氏病（AD）的新候选药物时，我们已经设计，合成和评估了一系列多功能三杂化剂。设计策略基于...
• 一种2-羧基哌嗪连接的他克林-8-氨基(羟基)喹啉衍生物及制备与应用
  申请人：广东工业大学

  公开号：CN110041309B

  公开（公告）日：2022-01-28

  本发明涉及化学合成技术领域，具体涉及一种2‑羧基哌嗪连接的他克林‑8‑氨基(羟基)喹啉衍生物及制备与应用。所述的2‑羧基哌嗪连接的他克林‑8‑氨基(羟基)喹啉衍生物，为式I化合物或其药学上可接受的盐，以及所述的式I化合物或其药学上可接受的盐的溶剂化合物、对映异构体、非对映异构体、互变异构体或其任意比例的混合物，包括外消旋混合物。经药理试验证实该类化合物对乙酰胆碱酯酶和丁酰胆碱酯酶活性具有抑制作用，属于胆碱酯酶抑制剂；并且还能对β‑淀粉样蛋白的自聚集产生抑制作用，对乙酰胆碱的水解和β‑淀粉样蛋白的自聚集起到延缓作用，进而提高了乙酰胆碱在突触的作用，最终实现有效治疗阿茨海默症的目的。
• AChE蛋白降解物及其制备方法和应用
  申请人：浙江省医学科学院

  公开号：CN110713480B

  公开（公告）日：2021-02-26

  本发明公开了一种AChE蛋白降解物及其制备方法和应用，为通式III或IV所示的结构。本发明将AChE配体与CRBN配体采用合适的手段连接，设计得到新的化合物，使其可以特异性地增强AChE的降解，从而达到治疗相关疾病的目的。该化合物及其药学上可接受的盐可用于制备乙酰胆碱酯酶降解中获益的疾病、障碍或病症药物。AChE降解增强化合物以其独有的诱导蛋白降解机制，而只需要少量的药物就可以，这个过程类似于催化反应，并不需要等摩尔量的药物，使用双功能小分子可以降低药物使用剂量，减轻毒副作用。
• Design, synthesis and neuroprotective evaluation of novel tacrine–benzothiazole hybrids as multi-targeted compounds against Alzheimer’s disease
  作者：Rangappa S. Keri、Catarina Quintanova、Sérgio M. Marques、A. Raquel Esteves、Sandra M. Cardoso、M. Amélia Santos

  DOI：10.1016/j.bmc.2013.05.028

  日期：2013.8

  Alzheimer's disease (AD) is a multifactorial disorder with several target proteins contributing to its etiology. In search for multifunctional anti-AD drug candidates, taking into account that the acetylcholinesterase (AChE) and beta-amyloid (A beta) aggregation are particularly important targets for inhibition, the tacrine and benzothiazole (BTA) moieties were conjugated with suitable linkers in a novel series of hybrids. The designed compounds (7a-7e) were synthesized and in vitro as well as in ex vivo evaluated for their capacity for the inhibition of acetylcholinesterase (AChE) and A beta self-induced aggregation, and also for the protection of neuronal cells death (SHSY-5Y cells, AD and MCI cybrids). All the tacrine-BTA hybrids displayed high in vitro activities, namely with IC50 values in the low micromolar to sub-micromolar concentration range towards the inhibition of AChE, and high percentages of inhibition of the self-induced A beta aggregation. Among them, compound 7a, with the shortest linker, presented the best inhibitory activity of AChE (IC50 = 0.34 mu M), while the highest activity as anti-A beta(42) self-aggregation, was evidenced for compound 7b (61.3%, at 50 mu M. The docking studies demonstrated that all compounds are able to interact with both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Our results show that compounds 7d and 7e improved cell viability in cells treated with A beta(42) peptide. Overall, these multi-targeted hybrid compounds appear as promising lead compounds for the treatment of Alzheimer's disease. (C) 2013 Elsevier Ltd. All rights reserved.
• Novel Tacrine−Melatonin Hybrids as Dual-Acting Drugs for Alzheimer Disease, with Improved Acetylcholinesterase Inhibitory and Antioxidant Properties
  作者：María Isabel Rodríguez-Franco、María Isabel Fernández-Bachiller、Concepción Pérez、Blanca Hernández-Ledesma、Begoña Bartolomé

  DOI：10.1021/jm050746d

  日期：2006.1.1

  Tacrine and melatonin are well-known drugs with activities as an acetylcholinesterase (AChE) inhibitor and free radical scavenger, respectively. In this work, we report new hybrids of both drugs that display higher in vitro properties than the sum of their parts. As selective inhibitors of human AChE, their IC50 values range from sub-nanomolar to picomolar. They exhibit a higher oxygen radical absorbance capacity than does melatonin and are predicted to be able to cross the blood-brain barrier to reach their targets in the central nervous system.