6,8-dichloro-1,2,3,4-tetrahydro-9-hydroxyacridine | 365533-82-0

• 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-dichloro-1,2,3,4-tetrahydro-9-hydroxyacridine
• 英文别名: 6,8-dichloro-9-hydroxy-1,2,3,4-tetrahydroacridine；6,8-Dichloro-1,2,3,4-tetrahydro-acridin-9-ol；6,8-dichloro-2,3,4,10-tetrahydro-1H-acridin-9-one
• CAS: 365533-82-0
• 化学式: C₁₃H₁₁Cl₂NO
• mdl: MFCD13477884
• 分子量: 268.142
• InChiKey: UZZQLXJKYBQUCC-UHFFFAOYSA-N

物化性质

• 沸点：
  449.0±45.0 °C(Predicted)
• 密度：
  1.442±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6,8-dichloro-1,2,3,4-tetrahydro-9-hydroxyacridine 在 三氯氧磷 作用下， 反应 0.75h， 以87%的产率得到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
• 作为产物：
  描述：

  2,4-二氯苯胺 以 二苯醚 为溶剂， 反应 8.42h， 生成 6,8-dichloro-1,2,3,4-tetrahydro-9-hydroxyacridine
  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。
• Optimization of 1,2,3,4-Tetrahydroacridin-9(10<i>H</i>)-ones as Antimalarials Utilizing Structure–Activity and Structure–Property Relationships
  作者：R. Matthew Cross、Jordany R. Maignan、Tina S. Mutka、Lisa Luong、Justin Sargent、Dennis E. Kyle、Roman Manetsch

  DOI：10.1021/jm200015a

  日期：2011.7.14

  Antimalarial activity of 1,2,3,4-tetrahydroacridin-9(10H)-ones (THAs) has been known since the 1940s and has garnered more attention with the development of the acridinedione floxacrine (1) in the 1970s and analogues thereof such as WR 243251 (2a) in the 1990s. These compounds failed just prior to clinical development because of suboptimal activity, poor solubility, and rapid induction of parasite resistance. Moreover, detailed structure-activity relationship (SAR) studies of the THA core scaffold were lacking and SPR studies were nonexistent. To improve upon initial findings, several series of 1,2,3,4-tetrahydroacridin-9(10H)-ones were synthesized and tested in a systematic fashion, examining each compound for antimalarial activity, solubility, and permeability. Furthermore, a select set of compounds was chosen for microsomal stability testing to identify physicochemical liabilities of the THA scaffold. Several potent compounds (EC50 < 100 nM) were identified to be active against the clinically relevant isolates W2 and TM90-C2B while possessing good physicochemical properties and little to no cross-resistance.
• 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.
• ANTAGONISTES NPY, PREPARATION ET UTILISATIONS
  申请人：Cerep

  公开号：EP1879887A2

  公开（公告）日：2008-01-23