9-[(6-bromooctyl)amino]-6-chloro-1,2,3,4-tetrahydroacridine

• 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: 9-[(6-bromooctyl)amino]-6-chloro-1,2,3,4-tetrahydroacridine
• 英文别名: N-(8-bromooctyl)-6-chloro-1,2,3,4-tetrahydroacridin-9-amine；(8-Bromo-octyl)-(6-chloro-1,2,3,4-tetrahydro-acridin-9-yl)-amine
• 化学式: C₂₁H₂₈BrClN₂
• 分子量: 423.824
• InChiKey: XHRLFBZRRHMMGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-[(6-bromooctyl)amino]-6-chloro-1,2,3,4-tetrahydroacridine 、 Bonducellin 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 12.0h， 以75%的产率得到(E)-7-(8-(6-chloro-1,2,3,4-tetrahydroacridin-9-ylamino)hexyloxy)-3-(4-methoxybenzylidene)chroman-4-one
  参考文献：
  名称：

  Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine–Homoisoflavonoid hybrids

  摘要：

  A series of Tacrine-Homoisoflavonoid hybrids were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and human monoamine oxidases (MAOs). Most of the compounds were found to be potent against both ChEs and MAO-B. Among these hybrids, compound 8b, with a 6 carbon linker between tacrine and (E)-7-hydroxy-3-(4-methoxybenzylidene)chroman-4-one, proved to be the most potent against AChE and MAO-B with IC50 values of 67.9 nM and 0.401 mu M, respectively. This compound was observed to cross the blood-brain barrier (BBB) in a parallel artificial membrane permeation assay for the BBB (PAMPA-BBB). The results indicated that compound 8b is an excellent multifunctional promising compound for development of novel drugs for Alzheimer's disease (AD). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.050
• 作为产物：
  描述：

  2-氨基-4-氯苯腈 在 potassium hydroxide 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 52.0h， 生成 9-[(6-bromooctyl)amino]-6-chloro-1,2,3,4-tetrahydroacridine
  参考文献：
  名称：

  Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine–Homoisoflavonoid hybrids

  摘要：

  A series of Tacrine-Homoisoflavonoid hybrids were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and human monoamine oxidases (MAOs). Most of the compounds were found to be potent against both ChEs and MAO-B. Among these hybrids, compound 8b, with a 6 carbon linker between tacrine and (E)-7-hydroxy-3-(4-methoxybenzylidene)chroman-4-one, proved to be the most potent against AChE and MAO-B with IC50 values of 67.9 nM and 0.401 mu M, respectively. This compound was observed to cross the blood-brain barrier (BBB) in a parallel artificial membrane permeation assay for the BBB (PAMPA-BBB). The results indicated that compound 8b is an excellent multifunctional promising compound for development of novel drugs for Alzheimer's disease (AD). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.050

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。
• Synthesis and Pharmacological Evaluation of Huprine−Tacrine Heterodimers:  Subnanomolar Dual Binding Site Acetylcholinesterase Inhibitors
  作者：Pelayo Camps、Xavier Formosa、Diego Muñoz-Torrero、Julien Petrignet、Albert Badia、M. Victòria Clos

  DOI：10.1021/jm0496741

  日期：2005.3.1

  heterodimers has been developed by connection of huprine Y, a compound with one of the highest affinities for the active site of acetylcholinesterase yet reported, with tacrine, a compound with known affinity for the peripheral site of the enzyme, through a linker of appropriate length to allow simultaneous interaction with both binding sites. These compounds exhibit human acetylcholinesterase and butyrylcholinesterase

  通过将huprine Y（一种对乙酰胆碱酯酶活性位点具有最高亲和力的化合物）与tacrine（一种对酶的外围位点具有已知亲和力的化合物）相连接，开发了一系列的huprine-tacrine异二聚体。具有适当长度的接头，以允许同时与两个结合位点相互作用。这些化合物表现出人类乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性，其IC（50）值分别在亚纳摩尔和低纳摩尔范围内。
• US7605265B2
  申请人：——

  公开号：US7605265B2

  公开（公告）日：2009-10-20
• [EN] HETERODIMERS AND METHODS OF USING THEM<br/>[FR] HÉTÉRODIMÈRES ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：BIOTECHNOLOGY RES CORP LTD

  公开号：WO2008091901A1

  公开（公告）日：2008-07-31

  [EN] 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.
  [FR] La présente invention concerne de nouveaux hétérodimères de tétrahydroacridines et de tétrahydroquinolinones. Ces hétérodimères peuvent à la fois servir d'inhibiteurs d'acétylcholinestérase et d'antagonistes de récepteur de N-méthyl-D-aspartate (NMDA). Lesdits hétérodimères peuvent être utilisés pour améliorer des déficits cognitifs par le biais d'un traitement ou d'une prévention à la fois chez les êtres humains et les non-humains.
• Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine–Homoisoflavonoid hybrids
  作者：Yang Sun、Jianwen Chen、Xuemin Chen、Ling Huang、Xingshu Li

  DOI：10.1016/j.bmc.2013.09.050

  日期：2013.12

  A series of Tacrine-Homoisoflavonoid hybrids were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and human monoamine oxidases (MAOs). Most of the compounds were found to be potent against both ChEs and MAO-B. Among these hybrids, compound 8b, with a 6 carbon linker between tacrine and (E)-7-hydroxy-3-(4-methoxybenzylidene)chroman-4-one, proved to be the most potent against AChE and MAO-B with IC50 values of 67.9 nM and 0.401 mu M, respectively. This compound was observed to cross the blood-brain barrier (BBB) in a parallel artificial membrane permeation assay for the BBB (PAMPA-BBB). The results indicated that compound 8b is an excellent multifunctional promising compound for development of novel drugs for Alzheimer's disease (AD). (C) 2013 Elsevier Ltd. All rights reserved.