3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo<2.2.2>octane | 114724-64-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo<2.2.2>octane
• 英文别名: 3-(3-methyl-1,2,4-oxadiazol-5-yl)quinuclidine；L658,903；(+/-) 3-(3-Methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo [2.2.2]octane；3-(3-Methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo [2.2.2]octane；3-methyl-5-(quinuclidin-3-yl)-1,2,4-oxadiazole；1-Azabicyclo[2.2.2]octane, 3-(3-methyl-1,2,4-oxadiazol-5-yl)-；5-(1-azabicyclo[2.2.2]octan-3-yl)-3-methyl-1,2,4-oxadiazole
• CAS: 114724-64-0
• 化学式: C₁₀H₁₅N₃O
• 分子量: 193.249
• InChiKey: CJZKUTNGRZKBRH-UHFFFAOYSA-N

物化性质

• 沸点：
  316.3±44.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-Aza-bicyclo[2.2.2]octane-3-carboxylic acid [1-dimethylamino-eth-(E)-ylidene]-amide 在 sodium hydroxide 、 盐酸羟胺 、 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo<2.2.2>octane
  参考文献：
  名称：

  比较氮杂双环酯和恶二唑作为毒蕈碱受体的配体。

  摘要：

  与阿尔茨海默氏型痴呆症相关的认知缺陷与疾病中胆碱能功能的丧失之间的联系为检查毒蕈碱激动剂作为潜在治疗剂提供了基础。本文描述了新型的氮杂双环甲酯作为毒蕈碱受体配体的设计和合成。用3-甲基-1,2,4-恶二唑环取代甲酯可产生有效的代谢更稳定的毒蕈碱激动剂，能够穿透中枢神经系统。这些化合物相对于相应的甲酯通常显示出改善的亲和力。3-甲基1,2,4-恶二唑7b的亲和力是乙酰胆碱的4倍。关于氮杂双环的大小和几何形状以及杂芳族环的电子性质，讨论了受体亲和力。

  DOI：

  10.1021/jm00113a009

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS FOR COGNITION-ENHANCEMENT, METHODS OF MAKING, AND METHODS OF TREATING<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR AMÉLIORER LA FONCTION COGNITIVE, PROCÉDÉS DE FABRICATION ET MÉTHODES DE TRAITEMENT
  申请人：MITHRIDION INC

  公开号：WO2010102218A1

  公开（公告）日：2010-09-10

  Muscarinic agonists, which are useful for stimulating muscarinic receptors and treating cognitive disorders, are provided. Methods of synthesizing such agonists also are provided. Also provided are compositions for enhancing cognitive function in subjects such as humans, the compositions comprising a muscarinic agonist or a pharmaceutically suitable form thereof. Also provided are methods of treating animals such as humans by administering such compositions.

  提供了用于刺激肌气受体并治疗认知障碍的肌气受体激动剂。还提供了合成这类激动剂的方法。还提供了用于增强人类等受试者认知功能的组合物，该组合物包括肌气受体激动剂或其药用适宜形式。还提供了通过给予这类组合物来治疗动物如人类的方法。
• [EN] COMPOUNDS AND COMPOSITIONS FOR COGNITION-ENHANCEMENT, METHODS OF MAKING, AND METHODS OF TREATING<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR L'AMÉLIORATION DE LA COGNITION, LEURS PROCÉDÉS DE FABRICATION, ET MÉTHODES DE TRAITEMENT
  申请人：MITHRIDION INC

  公开号：WO2011085406A1

  公开（公告）日：2011-07-14

  Disclosed are muscarinic agonist compounds including oxadiazole derivatives, compositions and preparations thereof. Also disclosed are methods of synthesizing such oxadiazole compounds. Further disclosed are methods for treating a subject with said muscarinic agonists or a pharmaceutically suitable form thereof to enhance cognitive function.

  揭示了包括噻唑二唑衍生物在内的肌碱激动剂化合物，以及其组合物和制剂。还揭示了合成这种噻唑二唑化合物的方法。进一步揭示了使用这些肌碱激动剂或其药学适宜形式来增强认知功能的治疗方法。
• Novel quinuclidine-based ligands for the muscarinic cholinergic receptor
  作者：John Saunders、Mark Cassidy、Stephen B. Freedman、Elizabeth A. Harley、Leslie L. Iversen、Clare Kneen、Angus M. MacLeod、Kevin J. Merchant、Roger J. Snow、Raymond Baker

  DOI：10.1021/jm00166a008

  日期：1990.4

  been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent

  最近对阿尔茨海默氏病患者的临床研究表明，只有对毒蕈碱样皮质受体表现出高功效的药物才能产生令人鼓舞的结果。本文介绍了新型奎宁环胺基毒蕈碱激动剂的设计，合成和生化特性，这些激动剂可以轻松渗透到中枢神经系统中，并且能够在皮质部位发挥高效作用。通过使用能够测量受体亲和力并预测皮质功效的生化测定法，已发现恶二唑环和相关的杂环可以作为在几种已知毒蕈碱配体中发现的酯部分的生物立体替代物。在这一系列化合物中，存在的化合物的功效范围从高效激动剂到部分激动剂，再到具有与传统季铵配体相当或更高亲和力的拮抗剂。与最近的分子生物学研究一致，结构活性趋势是根据激动剂和拮抗剂的独立结合位点来解释的，其中H-键相互作用表征激动剂行为，而亲脂性结合表征拮抗剂行为。因此，氨基恶二唑部分具有针对激动剂分布进行优化的结构特征。根据激动剂和拮抗剂的单独结合位点来解释结构活性趋势，其中H-键相互作用表征激动剂行为，而亲脂性结合表征拮
• COMPOUNDS AND COMPOSITIONS FOR COGNITION-ENHANCEMENT, METHODS OF MAKING, AND METHODS OF TREATING
  申请人：Twose Trevor M.

  公开号：US20120046273A1

  公开（公告）日：2012-02-23

  Muscarinic agonists, which are useful for stimulating muscarinic receptors and treating cognitive disorders, are provided. Methods of synthesizing such agonists also are provided. Also provided are compositions for enhancing cognitive function in subjects such as humans, the compositions comprising a muscarinic agonist or a pharmaceutically suitable form thereof. Also provided are methods of treating animals such as humans by administering such compositions.

  提供了用于刺激毒蕈碱受体和治疗认知障碍的毒蕈碱激动剂。还提供了合成这种激动剂的方法。还提供了用于增强人类等受试者认知功能的组合物，其中组合物包括毒蕈碱激动剂或其药学上适宜的形式。还提供了通过给予这样的组合物治疗人类等动物的方法。
• Cognition Enhancing Compounds and Compositions, Methods of Making, and Methods of Treating
  申请人：Mithridion, Inc.

  公开号：US20130274299A1

  公开（公告）日：2013-10-17

  The invention relates generally to muscarinic agonists, which are useful for stimulating muscarine receptors, and treating cognitive disorders. Included among the muscarinic agonists disclosed herein are oxadiazole derivatives, compositions, and preparations thereof. Methods of synthesizing oxadiazole compounds also are provided. This disclosure also relates in part to compositions for enhancing cognitive function in subjects such as humans, the compositions comprising a muscarinic agonist or a pharmaceutically suitable form thereof. This disclosure relates in part to methods of treating animals such as humans by administering such compositions.

  本发明涉及肌肉碱受体激动剂，其可用于刺激肌肉碱受体和治疗认知障碍。本文所披露的肌肉碱受体激动剂包括噁唑烷衍生物、组合物及其制备。还提供了合成噁唑烷化合物的方法。本公开还涉及用于增强人类等受试者认知功能的组合物，该组合物包括肌肉碱受体激动剂或其药学适宜形式。本公开还涉及通过给予该类组合物治疗动物，如人类的方法。