2-(吡啶-3-基甲基)奎宁环-3-酮 | 273748-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 中文名称: 2-(吡啶-3-基甲基)奎宁环-3-酮
• 英文名称: 2-(3-pyridylmethyl)quinuclidin-3-one
• 英文别名: 2-((pyridin-3-yl)methyl)-1-azabicyclo[2.2.2]octan-3-one；2-(Pyridin-3-ylmethyl)quinuclidin-3-one；2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-one
• CAS: 273748-51-9
• 化学式: C₁₃H₁₆N₂O
• 分子量: 216.283
• InChiKey: RDZRUHBKCNPOPR-UHFFFAOYSA-N

物化性质

• 沸点：
  369.0±22.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 储存条件：
  存放条件：室温、密封、干燥

反应信息

• 作为反应物：
  描述：

  2-(吡啶-3-基甲基)奎宁环-3-酮 在 ammonium acetate 、 sodium cyanotrihydroborate 、 zinc(II) chloride 作用下， 以 甲醇 为溶剂， 反应 16.33h， 以90%的产率得到(±)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-amine
  参考文献：
  名称：

  靶向乙酰胆碱酯酶和α7烟碱乙酰胆碱受体的多功能配体的功能表征

  摘要：

  阿尔茨海默氏病（AD）是一种与老年人胆碱能功能障碍，诱发记忆力减退和认知功能障碍有关的神经退行性疾病。多年来，胆碱能假说为发展针对AD的姑息治疗提供了分子靶点，该药物作用于胆碱能系统，即乙酰胆碱酯酶和α7烟碱乙酰胆碱受体（α7nAChR）。在我们的合成工作中，我们使用“点击化学”来合成两个带有他克林和奎尼丁支架的多目标定向配体（MBDL）MB105和MB118，它们分别以其抗胆碱酯酶和α7烟碱型乙酰胆碱受体激动剂活性而著称。MB105和MB118均在纳摩尔范围内抑制人乙酰胆碱酯酶和人丁酰胆碱酯酶。表达人α7nAChR的非洲爪蟾卵母细胞的电生理记录表明，尽管MB105和MB118尽管结构相似，但它们还是所提及烟碱样受体的部分激动剂，尽管具有不同的效价。与MB105相比，2,3-二取代的奎宁环骨架上C-3处的不同取代可解释MB118的效力显着降低。电生理记录表明，他克林前体MB320在微摩尔范

  DOI：

  10.1016/j.bcp.2020.114010
• 作为产物：
  描述：

  3-奎宁环酮 在 palladium on activated charcoal 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 28.5h， 生成 2-(吡啶-3-基甲基)奎宁环-3-酮
  参考文献：
  名称：

  1,4-DISUBSTITUTED 1,2,3-TRIAZOLES, METHODS FOR PREPARING SAME, AND DIAGNOSTIC AND THERAPEUTIC USES THEREOF

  摘要：

  具有以下通式（I）的化合物：其中：X是氮原子，Y是碳原子；或者X是碳原子，Y是氮原子；Ar基团是芳基或杂芳基；RN和RN′基团，与其所连接的碳原子一起，形成单环或双环氮杂环烷基团。还描述了其药学上可接受的盐、水合物或多晶型晶体结构，以及其消旋体、非对映异构体或对映异构体。

  公开号：

  US20140030191A1

文献信息

• 2S,3R)-N-(2-((3-PYRIDINYL)METHYL)-1-AZABICYCLO[2.2.2]OCT-3-YL-BENZYOFURAN-2-CARBOXAMIDE, NOVEL SALT FORMS, AND METHODS OF USE THEREOF
  申请人：Bencherif Merouane

  公开号：US20090048290A1

  公开（公告）日：2009-02-19

  The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central and autonomic nervous systems.

  本发明涉及（2S,3R）-N-(2-((3-吡啶基)甲基)-1-氮杂双环[2.2.2]辛-3-基)苯并呋喃-2-甲酰胺，其新型盐形式，其制备方法，新型中间体以及治疗多种疾病和紊乱的方法，包括与中枢神经系统和自主神经系统功能障碍有关的疾病。
• 3-Substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof
  申请人：——

  公开号：US20040002513A1

  公开（公告）日：2004-01-01

  The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The aryl group in the arylalkyl moiety is a 5- or 6-membered ring heteroaromatic, preferably 3-pyridinyl and 5-pyrimidinyl moieties, and the alkyl group is typically a C 1-4 alkyl. The substituent at the 3-position of the 1-azabicycloalkane is a carbonyl group-containing moiety, such as an amide, carbamate, urea, thioamide, thiocarbamate, thiourea or similar functionality. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the &agr;7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission. Methods for preventing or treating conditions and disorders, including central nervous system (CNS) disorders, which are characterized by an alteration in normal neurotransmission, are also disclosed. Also disclosed are methods for treating inflammation, autoimmune disorders, pain and excess neovascularization, such as that associated with tumor growth.

  本发明涉及3-取代-2-(芳基烷基)-1-氮杂双环烷类化合物，制备这些化合物的方法以及使用这些化合物进行治疗的方法。这些氮杂双环烷通常是氮杂双环庚烷、氮杂双环辛烷或氮杂双环壬烷。芳基烷基中的芳基是一个5-或6-成员环杂芳基，优选是3-吡啶基和5-嘧啶基，烷基通常是C1-4烷基。1-氮杂双环烷的3-位取代基是一个含有羰基的基团，例如酰胺、碳酸酯、脲、硫代酰胺、硫代碳酸酯、硫脲或类似功能基团。这些化合物在尼古丁型乙酰胆碱受体(nAChRs)上表现出活性，特别是α7 nAChR亚型，并且对调节神经递质传递和与神经递质有关的配体释放具有用处。还公开了用于预防或治疗中枢神经系统（CNS）疾病等疾病和疾病的方法，这些疾病和疾病以正常神经递质传递的改变为特征。还公开了用于治疗炎症、自身免疫疾病、疼痛和过度新生血管化的方法，例如与肿瘤生长相关的新生血管化。
• ANTIPRURITIC AGENT
  申请人：Hayashi Kenichi

  公开号：US20140128606A1

  公开（公告）日：2014-05-08

  An antipruritic which exerts an antipruritic effect based on a novel action mechanism and is effective for pruritus. The antipruritic contains as an effective ingredient a compound which activates a central type nicotinic acetylcholine receptor.

  一种抗瘙痒药物，基于新颖的作用机制发挥抗瘙痒作用，并对瘙痒有效。该抗瘙痒药物含有一种有效成分，该成分可以激活中枢型尼古丁乙酰胆碱受体。
• Discovery of (2<i>S</i>,3<i>R</i>)-<i>N</i>-[2-(Pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[<i>b</i>]furan-2-carboxamide (TC-5619), a Selective α7 Nicotinic Acetylcholine Receptor Agonist, for the Treatment of Cognitive Disorders
  作者：Anatoly A. Mazurov、David C. Kombo、Terry A. Hauser、Lan Miao、Gary Dull、John F. Genus、Nikolai B. Fedorov、Lisa Benson、Serguei Sidach、Yunde Xiao、Philip S. Hammond、John W. James、Craig H. Miller、Daniel Yohannes

  DOI：10.1021/jm301048a

  日期：2012.11.26

  (2S,3R)-N-[2-(Pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]-furan-2-carboxamide (7a, TC-561), a novel selective agonist Of the alpha 7 neuronal nicotinic acetylcholine receptor, has been as a promising drug candidate for the treatment of.cognitiVe. impairment 'associated with neurological.. disorders demonstrated more than a thousand fold separation between the affinities for the alpha 7 and alpha 4 beta 2 receptor subtypes and had no detectable effects On muscle or ganglionic nicotinic receptor subtypes, indicating a marked selectivity for the central nervous system over the peripheral nervous system. Results obtained from homology Modeling and docking explain the observed selectivity. 7a had positive effects cognitive, positive, negative symptoms of schizophrenia in animal models and was additive or synergistic with the antipsychotic. Clozapine. Compound 7a, as an augmentation: therapy to the standard treatment with antipsychotics, demonstrated encouraging results on measures. : of negative symptoms and cognitive dysfunction in schizophrenia and was well tolerated.: in a phase II clinical proof Of concept trial in patients With Schizophrenia.

  (2S,3R)-N-[2-(Pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]-furan-2-carboxamide（7a，TC-561）是一种新型选择性α7神经性烟碱型乙酰胆碱受体激动剂。它作为一种有前景的药物候选物，用于治疗与神经系统疾病相关的认知功能障碍。其对α7和α4β2受体亚型的亲和力分离系数超过千倍，并对肌肉或节交感神经烟碱型受体亚型无可检测到的影响，表明其对中枢神经系统相对于外周神经系统的显著选择性。 通过同源建模和对接研究获得的结果解释了观察到的选择性。在动物模型中，7a对认知功能、精神分裂症的阳性症状和阴性症状均表现出积极效果，并与抗精神病药物Clozapine表现出叠加或协同作用。在II期临床概念验证试验中，化合物7a作为标准抗精神病药物治疗的辅助疗法，在改善精神分裂症患者的阴性症状和认知功能障碍方面表现出令人鼓舞的结果，并且耐受性良好。
• 3-substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof
  申请人：Mazurov Anatoly A.

  公开号：US06953855B2

  公开（公告）日：2005-10-11

  The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The aryl group in the arylalkyl moiety is a 5- or 6-membered ring heteroaromatic, preferably 3-pyridinyl and 5-pyrimidinyl moieties, and the alkyl group is typically a C 1-4 alkyl. The substituent at the 3-position of the 1-azabicycloalkane is a carbonyl group-containing moiety, such as an amide, carbamate, urea, thioamide, thiocarbamate, thiourea or similar functionality. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission. Methods for preventing or treating conditions and disorders, including central nervous system (CNS) disorders, which are characterized by an alteration in normal neurotransmission, are also disclosed. Also disclosed are methods for treating inflammation, autoimmune disorders, pain and excess neovascularization, such as that associated with tumor growth.

  本发明涉及3-取代-2-(芳基烷基)-1-氮杂双环烷化合物，制备该化合物的方法以及使用该化合物的治疗方法。氮杂双环烷一般是氮杂七环烷、氮杂八环烷或氮杂壬环烷。芳基烷基中的芳基基团是一个5-或6-成员环杂芳基，优选为3-吡啶基和5-嘧啶基团，烷基通常是C1-4烷基。1-氮杂双环烷的3位取代基是含有羰基基团的官能团，例如酰胺、氨基甲酸酯、尿素、硫酰胺、硫代氨基甲酸酯、硫脲或类似的官能团。该化合物在尼古丁乙酰胆碱受体(nAChRs)特别是α7 nAChR亚型表现出活性，并且对调节神经递质和参与神经递质释放的配体的释放有用。还公开了预防或治疗中枢神经系统(CNS)疾病等特征为正常神经递质改变的疾病和疾病的方法。还公开了治疗炎症、自身免疫性疾病、疼痛和过度新生血管化的方法，例如与肿瘤生长有关的新生血管化。