2-[7-(1,2,3,4-tetrahydro-acridin-9-ylamino)-heptyl]-isoindole-1,3-dione

• 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: 2-[7-(1,2,3,4-tetrahydro-acridin-9-ylamino)-heptyl]-isoindole-1,3-dione
• 英文别名: 2-[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl]isoindole-1,3-dione
• 化学式: C₂₈H₃₁N₃O₂
• 分子量: 441.573
• InChiKey: DGQLSDQJMPNFLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-(7-bromoheptyl)phthalimide 、 四氢氨基吖啶 在 氢氧化钾 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 以5%的产率得到2-[7-(1,2,3,4-tetrahydro-acridin-9-ylamino)-heptyl]-isoindole-1,3-dione
  参考文献：
  名称：

  Donepezil–tacrine hybrid related derivatives as new dual binding site inhibitors of AChE

  摘要：

  A new series of donepezil-tacrine hybrid related derivatives have been synthesised as dual acetylcholinesterase inhibitors that could bind simultaneously to the peripheral and catalytic sites of the enzyme. These new hybrids combined a tacrine, 6-chlorotacrine or acridine unit as catalytic binding site and indanone (the heterocycle present in donepezil) or phthalimide moiety as peripheral binding site of the enzyme, connected through a different linker tether length. One of the synthesised compounds emerged as a potent and selective AChE inhibitor, which is able to displace propidium in a competition assay. These results seem to confirm the ability of this inhibitor to bind simultaneously to both sites of the enzyme and make it a promising lead for developing disease-modifying drugs for the future treatment of Alzheimer's disease. To gain insight into the molecular determinants that modulate the inhibitory activity of these compounds, a molecular modelling study was performed to explore their binding to the enzyme. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.09.029

文献信息

• Dual binding site acetylcholinesterase inhibitors for the treatment of alzheimer's disease
  申请人：Gil Martinez Ana

  公开号：US20060142323A1

  公开（公告）日：2006-06-29

  A family of compounds of formula (I) wherein: X is one of the following radicals: which behaves as dual site acetyl-cholinesterase inhibitors and which are especially useful for the treatment of cognitive disorders as senile dementia, cerebrovascular dementia, mild cognition impairment, attention deficit disorder, and/or neurodegenerative dementing disease with aberrant protein aggregations as specially Alzheimer's disease, Parkinson disease, ALS, or prion diseases, as Creutzfeldt-Jakob disease or Gerst-mann-Straussler-Scheiner disease.

  一种化合物家族的公式（I），其中：X是以下基团之一：这些基团表现为双位点乙酰胆碱酯酶抑制剂，特别适用于治疗认知障碍，如老年性痴呆症、脑血管性痴呆症、轻度认知障碍、注意力缺陷障碍和/或神经退行性痴呆性疾病，其中异常蛋白质聚集尤为突出，如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症或朊病，如克雅氏病或格斯特曼-斯特劳斯勒-谢因纳病。
• Methods and compositions for improving cognitive function
  申请人：AgeneBio, Inc.

  公开号：US11160785B2

  公开（公告）日：2021-11-02

  The invention relates to compositions comprising a synaptic vesicle glycoprotein 2A (SV2A) inhibitor in an extended release and an acetylcholinesterase inhibitor (AChEIs). The invention also relates to using such compositions in treating cognitive impairment associated with central nervous system disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism, compulsive behavior, and substance addiction.

  本发明涉及一种组合物，该组合物包含一种缓释的突触小泡糖蛋白 2A (SV2A) 抑制剂和一种乙酰胆碱酯酶抑制剂 (AChEIs)。本发明还涉及使用此类组合物治疗有需要或有风险的受试者与中枢神经系统疾病相关的认知障碍，包括但不限于具有或有风险的受试者与年龄相关的认知障碍、轻度认知障碍（MCI）、痴呆症、阿尔茨海默氏症（Alzheimer）、老年痴呆症（Dementia）、阿尔茨海默氏症（Alzheimer）等、痴呆症、阿尔茨海默病 (AD)、前驱 AD、创伤后应激障碍 (PTSD)、精神分裂症、双相情感障碍、肌萎缩性脊髓侧索硬化症 (ALS)、癌症治疗相关认知障碍、智力迟钝、帕金森病 (PD)、自闭症、强迫行为和药物成瘾。
• [EN] DUAL BINDING SITE ACETYLCHOLINESTERASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] INHIBITEURS D'ACETYLCHOLINESTERASE A SITE DE LIAISON DOUBLE DESTINES AU TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：NEUROPHARMA SA

  公开号：WO2004032929A3

  公开（公告）日：2004-07-01
• DUAL BINDING SITE ACETYLCHOLINESTERASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
  申请人：Neuropharma, S.A.

  公开号：EP1558255A2

  公开（公告）日：2005-08-03
• METHODS AND COMPOSITIONS FOR IMPROVING COGNITIVE FUNCTION
  申请人：The Johns Hopkins University

  公开号：EP2533645A1

  公开（公告）日：2012-12-19