3-amino-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octane | 1391013-37-8

• 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-amino-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octane
• 英文别名: 2-(Pyridin-3-ylmethyl)quinuclidin-3-amine；2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-amine
• CAS: 1391013-37-8
• 化学式: C₁₃H₁₉N₃
• 分子量: 217.314
• InChiKey: ZUCBDKDJRQVFNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-amino-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octane 在 D-(+)-二对甲基苯甲酰酒石酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]benzamide
  参考文献：
  名称：

  Discovery of (2S,3R)-N-[2-(Pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]furan-2-carboxamide (TC-5619), a Selective α7 Nicotinic Acetylcholine Receptor Agonist, for the Treatment of Cognitive Disorders

  摘要：

  (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。

  DOI：

  10.1021/jm301048a
• 作为产物：
  描述：

  生成 3-amino-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octane
  参考文献：
  名称：

  J. Med. Chem. 2012, 55, 9793-9809

  摘要：

  DOI：

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。
• 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、制备这些化合物的方法以及使用这些化合物的治疗方法。氮杂双环烷化合物通常是氮杂双环庚烷、氮杂双环辛烷或氮杂双环壬烷。芳基烷基中的芳基基团是一个5-或6-成员环的杂芳族，优选的是3-吡啶基和5-嘧啶基团，而烷基通常是C1-4烷基。1-氮杂双环烷的3-位取代基是一个含有羰基基团的基团，例如酰胺、氨基甲酸酯、脲、硫酰胺、硫代氨基甲酸酯、硫脲或类似的官能团。这些化合物在尼古丁乙酰胆碱受体(nAChRs)上表现出活性，特别是α7 nAChR亚型，并且有助于调节神经递质和神经递质中涉及的配体的释放。还公开了预防或治疗中枢神经系统(CNS)疾病等表现为正常神经递质改变的疾病和障碍的方法。还公开了治疗炎症、自身免疫性疾病、疼痛和过度新血管生成的方法，例如与肿瘤生长相关的过度新血管生成。
• 3-Substituted-2(Arylalkyl)-1-Azabicycloalkanes and Methods of Use Thereof
  申请人：Mazurov A. Anatoly

  公开号：US20060247270A1

  公开（公告）日：2006-11-02

  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。芳基烷基中的芳基基团是5-或6-成员环异芳基，优选为3-吡啶基和5-嘧啶基团，烷基通常为C1-4烷基。1-氮杂双环烷的3-位取代基是含有羰基基团的基团，例如酰胺、氨基甲酸酯、脲、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)上表现出活性，特别是α7 nAChR亚型，并对调节神经递质和参与神经递质释放的配体具有用处。还公开了预防或治疗中枢神经系统(CNS)疾病等条件和障碍的方法，这些疾病的特征是正常神经递质发生改变。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。
• 3-SUBSTITUTED-2(ARYLALKYL)-1- AZABICYCLOALKANES AND METHODS OF USE THEREOF
  申请人：Mazurov Anatoly A.

  公开号：US20080138287A1

  公开（公告）日：2008-06-12

  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-氮杂双环烷类化合物、制备该类化合物的方法以及使用该类化合物的治疗方法。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-位取代基是一种含有羰基基团的基团，例如酰胺、氨基甲酸酯、脲、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)上表现出活性，特别是α7 nAChR亚型，并且对于调节神经递质和神经递质参与的配体的释放是有用的。还公开了预防或治疗条件和疾病的方法，包括中枢神经系统(CNS)疾病，这些疾病的特征是正常神经递质的改变。还公开了治疗炎症、自身免疫性疾病、疼痛和过度新血管生成的方法，例如与肿瘤生长相关的新血管生成。