N-[6-(6-chloro-1,2,3,4-tetrahydro-acridin-9-ylamino)-hexyl]-3-(1H-indol-3-yl)-propionamide

• 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: N-[6-(6-chloro-1,2,3,4-tetrahydro-acridin-9-ylamino)-hexyl]-3-(1H-indol-3-yl)-propionamide
• 英文别名: N-[5-(6-Chloro-1,2,3,4-tetrahydroacridin-9-ylamino)-hexyl]-3-(1H-indol-3-yl)propionamide；N-[6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl]-3-(1H-indol-3-yl)propanamide
• 化学式: C₃₀H₃₅ClN₄O
• 分子量: 503.087
• InChiKey: CPLGYLJHIKGTTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  69.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N¹-(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)hexane-1,6-diamine 、 3-吲哚丙酸 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以77%的产率得到N-[6-(6-chloro-1,2,3,4-tetrahydro-acridin-9-ylamino)-hexyl]-3-(1H-indol-3-yl)-propionamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Dual Binding Site Acetylcholinesterase Inhibitors:  New Disease-Modifying Agents for Alzheimer's Disease

  摘要：

  New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as new potent drugs that may simultaneously alleviate cognitive deficits and behave as disease-modifying agents by inhibiting the P-amyloid (M) peptide aggregation through binding to both catalytic and peripheral sites of the enzyme. Particularly, compounds 5 and 6 emerged as the most potent heterodimers reported so far, displaying IC50 values for AChE inhibition of 20 and 60 pM, respectively. More importantly, these dual AChE inhibitors inhibit the AChE-induced A beta peptide aggregation with IC50 values 1 order of magnitude lower than that of propidium, thus being the most potent derivatives with this activity reported up to date. We therefore conclude that these compounds are very promising disease-modifying agents for the treatment of Alzheimer's disease (AD).

  DOI：

  10.1021/jm0503289

文献信息

• TACRINE DERIVATIVES AS INHIBITORS OF ACETYLCHOLINESTERASE
  申请人：NOSCIRA, S.A.

  公开号：EP1646622B1

  公开（公告）日：2010-11-03
• Design, Synthesis, and Biological Evaluation of Dual Binding Site Acetylcholinesterase Inhibitors:  New Disease-Modifying Agents for Alzheimer's Disease
  作者：Pilar Muñoz-Ruiz、Laura Rubio、Esther García-Palomero、Isabel Dorronsoro、María del Monte-Millán、Rita Valenzuela、Paola Usán、Celia de Austria、Manuela Bartolini、Vincenza Andrisano、Axel Bidon-Chanal、Modesto Orozco、F. Javier Luque、Miguel Medina、Ana Martínez

  DOI：10.1021/jm0503289

  日期：2005.11.1

  New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as new potent drugs that may simultaneously alleviate cognitive deficits and behave as disease-modifying agents by inhibiting the P-amyloid (M) peptide aggregation through binding to both catalytic and peripheral sites of the enzyme. Particularly, compounds 5 and 6 emerged as the most potent heterodimers reported so far, displaying IC50 values for AChE inhibition of 20 and 60 pM, respectively. More importantly, these dual AChE inhibitors inhibit the AChE-induced A beta peptide aggregation with IC50 values 1 order of magnitude lower than that of propidium, thus being the most potent derivatives with this activity reported up to date. We therefore conclude that these compounds are very promising disease-modifying agents for the treatment of Alzheimer's disease (AD).