carbonic acid 2-(1H-indol-3-yl)ethyl ester 4-nitrophenyl ester | 869301-36-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: carbonic acid 2-(1H-indol-3-yl)ethyl ester 4-nitrophenyl ester
• 英文别名: carbonic acid 2-(1H-indol-3-yl)-ethyl ester 4-nitro-phenyl ester；2-(1H-indol-3-yl)ethyl (4-nitrophenyl) carbonate
• CAS: 869301-36-0
• 化学式: C₁₇H₁₄N₂O₅
• 分子量: 326.309
• InChiKey: HMNJZFFLCHPGQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  carbonic acid 2-(1H-indol-3-yl)ethyl ester 4-nitrophenyl ester 、 4-(2-氨基乙基)-1-苄基哌啶 在 4-二甲氨基吡啶 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 24.0h， 以44%的产率得到[2-(1-benzyl-piperidin-4-yl)-ethyl]-carbamic acid 2-(1H-indol-3-yl)-ethyl ester
  参考文献：
  名称：

  Butyrylcholinesterase selective inhibitors

  摘要：

  该发明提供了公式I的丁酰胆碱酯酶抑制剂，其中包含一个杂环基团和一个带有连接物的4-哌啶基团。这些化合物对BuChE表现出非常高的活性和选择性，使它们在治疗和/或预防认知障碍和/或神经退行性疾病方面非常有用。

  公开号：

  EP1600447A1
• 作为产物：
  描述：

  色醇 、 对硝基苯基氯甲酸酯 在 N-甲基吗啉 作用下， 反应 24.0h， 以32%的产率得到carbonic acid 2-(1H-indol-3-yl)ethyl ester 4-nitrophenyl ester
  参考文献：
  名称：

  Butyrylcholinesterase selective inhibitors

  摘要：

  该发明提供了公式I的丁酰胆碱酯酶抑制剂，其中包含一个杂环基团和一个带有连接物的4-哌啶基团。这些化合物对BuChE表现出非常高的活性和选择性，使它们在治疗和/或预防认知障碍和/或神经退行性疾病方面非常有用。

  公开号：

  EP1600447A1

文献信息

• [EN] TACRINE DERIVATIVES AS INHIBITORS OF ACETYLCHOLINESTERASE<br/>[FR] DERIVES DE TACRINE UTILISES EN TANT QU'INHIBITEURS DE L'ACETYLCHOLINESTERASE
  申请人：NEUROPHARMA SA

  公开号：WO2005005413A1

  公开（公告）日：2005-01-20

  The invention provides compounds of formula: (I) which have a tacrine moiety connected to an heterocyclic moiety through a linker. Through careful selection of the substituents and the linker, the activity and selectivity towards acetylcholinesterase can be modulated. The compounds show potent AChE inhibition activities together with modifications in the beta-amyloid aggregation properties by binding simultaneously to the catalytic and peripheral AChE sites. They are useful in the treatment of AChE mediated diseases, such as the Alzheimer's disease.

  该发明提供了具有以下公式的化合物：（I），其中通过连接剂将一种他环境基团连接到一种杂环基团。通过精心选择取代基和连接剂，可以调节对乙酰胆碱酯酶的活性和选择性。这些化合物显示出强大的AChE抑制活性，同时通过同时结合催化和外周AChE位点，改变了β-淀粉样蛋白聚集特性。它们在治疗AChE介导的疾病，如阿尔茨海默病中非常有用。
• Acetylcholinesterase dual inhibitors
  申请人：Gil Martinez Ana

  公开号：US20050148621A1

  公开（公告）日：2005-07-07

  The invention provides compounds of formula: which have a tacrine moiety connected to an heterocyclic moiety through a linker. Through careful selection of the substituents and the linker, the activity and selectivity towards acetylcholinesterase can be modulated. The compounds show potent AChE inhibition activities together with modifications in the β-amyloid aggregation properties by binding simultaneously to the catalytic and peripheral AChE sites. They are useful in the treatment of AChE mediated diseases, such as the Alzheimer's disease.

  该发明提供了公式的化合物：其中通过连接剂连接了一种Tacrine基团和一个杂环基团。通过精心选择取代基和连接剂，可以调节对乙酰胆碱酯酶的活性和选择性。这些化合物显示出强大的AChE抑制活性，同时通过同时结合催化和周围AChE位点，修改β淀粉样聚集物的聚集特性。它们在治疗AChE介导的疾病，如阿尔茨海默病中很有用。
• Butyrlcholinesterase Selective Inhibitors
  申请人：Martinez Gil Ana

  公开号：US20080119521A1

  公开（公告）日：2008-05-22

  The invention provides butyrylcholinesterase inhibitors of formula (I), which contain an heterocyclic moiety and a 4 piperidine moiety with a linker in between. The compounds show a very high activity and selectivity towards BuChE, making them useful for the treatment and/or prophylaxis of cognitive disorders and/or neurodegenerative disorders.

  该发明提供了具有公式(I)的丁酰胆碱酯酶抑制剂，其中包含杂环基团和4-哌啶基团，并在两者之间具有连接基。这些化合物对BuChE表现出非常高的活性和选择性，因此它们可用于治疗和/或预防认知障碍和/或神经退行性疾病。
• ACETYLCHOLINESTERASE DUAL INHIBITORS
  申请人：Gil Ana Martinez

  公开号：US20110144148A1

  公开（公告）日：2011-06-16

  The invention provides compounds of formula: which have a tacrine moiety connected to an heterocyclic moiety through a linker. Through careful selection of the substituents and the linker, the activity and selectivity towards acetylcholinesterase can be modulated. The compounds show potent AChE inhibition activities together with modifications in the β-amyloid aggregation properties by binding simultaneously to the catalytic and peripheral AChE sites. They are useful in the treatment of AChE mediated diseases, such as the Alzheimer's disease.

  本发明提供了公式如下的化合物: 通过连接剂将Tacrine基团连接到杂环基团上。通过对取代基和连接剂的精心选择，可以调节其对乙酰胆碱酯酶的活性和选择性。这些化合物表现出强效的AChE抑制活性，并通过同时结合催化和周边AChE位点来改变β-淀粉样聚集物的聚集特性。它们在治疗AChE介导的疾病，如阿尔茨海默病方面非常有用。
• 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).