6,8,9-trichloro-1,2,3,4-tetrahydroacridine | 365533-85-3

• 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: 6,8,9-trichloro-1,2,3,4-tetrahydroacridine
• 英文别名: 6,8,9-Trichloro-1,2,3,4-tetrahydro-acridine
• CAS: 365533-85-3
• 化学式: C₁₃H₁₀Cl₃N
• 分子量: 286.588
• InChiKey: RVQDBDPTAJTNAP-UHFFFAOYSA-N

物化性质

• 沸点：
  418.1±45.0 °C(Predicted)
• 密度：
  1.436±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6,8,9-trichloro-1,2,3,4-tetrahydroacridine 在 sodium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 7-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]heptanamide
  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
• 作为产物：
  描述：

  2,4-二氯苯胺 在 三氯氧磷 作用下， 以 二苯醚 为溶剂， 反应 9.17h， 生成 6,8,9-trichloro-1,2,3,4-tetrahydroacridine
  参考文献：
  名称：

  Specific Targeting of Acetylcholinesterase and Butyrylcholinesterase Recognition Sites. Rational Design of Novel, Selective, and Highly Potent Cholinesterase Inhibitors

  摘要：

  Tacrine-based AChE and BuChE inhibitors were designed by investigating the topology of the active site gorge of the two enzymes. The homobivalent ligands characterized by a nitrogen-bridged atom at the tether level could be considered among the most potent and selective cholinesterase inhibitors described to date. The nitrogen-containing homobivalent ligands 3e,g and the sulfur-containing 3h validated the hypothesis of extra sites of interaction in the AChE and BuChE active site gorges.

  DOI：

  10.1021/jm0255668

文献信息

• Heterodimers and Methods of Using Them
  申请人：IP Nancy Y.

  公开号：US20080176308A1

  公开（公告）日：2008-07-24

  Novel heterodimers of tetrahydroacridines and tetrahydroquinolinones are disclosed. The heterodimers are capable of acting as both acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. The heterodimers may be used to improve cognitive defects via treatment or prevention in both humans and non-humans.

  揭示了新型四氢喹啉和四氢喹啉酮的异源二聚体。这些异源二聚体能够同时作为乙酰胆碱酯酶抑制剂和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。这些异源二聚体可用于改善人类和非人类的认知缺陷，通过治疗或预防。
• Heterodimers and methods of using them
  申请人：Biotechnology Research Corporation Ltd.

  公开号：US07605265B2

  公开（公告）日：2009-10-20

  Novel heterodimers of tetrahydroacridines and tetrahydroquinolinones are disclosed. The heterodimers are capable of acting as both acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. The heterodimers may be used to improve cognitive defects via treatment or prevention in both humans and non-humans.

  本发明揭示了四氢喹啉酮和四氢咯啉酸的新型杂二聚物。这些杂二聚物既能作为乙酰胆碱酯酶抑制剂，又能作为N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂。这些杂二聚物可用于治疗或预防人类和非人类的认知缺陷。
• A tetrahydroacridine derivative and its conjugate with gold nanoparticles: promising agents for the treatment of Alzheimer's disease
  作者：Ilona Mojzych、Anna Zawadzka、Katarzyna Kaczyńska、Piotr Wojciechowski、Dominika Zając、Maciej Chotkowski、Katarzyna Wiktorska、Jan K. Maurin、Maciej Mazur

  DOI：10.1039/d3cp00767g

  日期：——

  fluorescence, which is effectively quenched after adsorption onto gold via a static quenching mechanism. Both CHDA and its conjugate reveal considerable inhibitory properties against acetylcholinesterase activity, which is promising from the perspective of therapeutic application in the treatment of Alzheimer's disease. Moreover, both agents appear to be non-toxic as demonstrated using in vitro studies

  合成了一种具有乙酰胆碱酯酶抑制特性的新型四氢吖啶衍生物（CHDA）。使用一系列物理化学技术，结果表明该化合物强烈吸附在平面宏观或纳米颗粒金的表面，形成几乎完整的单层。吸附的 CHDA 分子显示出明确的电化学行为，被不可逆地氧化为电活性物质。CHDA还表现出强烈的荧光，通过吸附到金上后被有效猝灭。静态淬火机制。CHDA 及其缀合物都显示出对乙酰胆碱酯酶活性的相当大的抑制特性，从治疗阿尔茨海默氏病的治疗应用的角度来看，这是有希望的。此外，体外研究证明这两种药物似乎都是无毒的。另一方面，CHDA 与纳米放射金颗粒 (Au-198) 的结合为医学成像提供了新的潜在诊断前景。
• Novel and potent tacrine-related hetero- and homobivalent ligands for acetylcholinesterase and butyrylcholinesterase
  作者：Luisa Savini、Giuseppe Campiani、Alessandra Gaeta、Cesare Pellerano、Caterina Fattorusso、Luisa Chiasserini、James M Fedorko、Ashima Saxena

  DOI：10.1016/s0960-894x(01)00294-3

  日期：2001.7

  Based upon synthetic and biochemical results, a novel and potent tacrine analogue and heterobivalent analogues of tacrine, were designed. The role played by the amino groups of homo- and heterobivalent ligands in the interaction with the peripheral and catalytic sites of AChE and BuChE were investigated. The syntheses of these materials together with the results of AChE/BuChE inhibition assays are detailed. (C) 2001 Elsevier Science Ltd. All rights reserved.
• US7605265B2
  申请人：——

  公开号：US7605265B2

  公开（公告）日：2009-10-20