cis-2-(3-pyridylmethyl)-3-quinuclidinol

• 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: cis-2-(3-pyridylmethyl)-3-quinuclidinol
• 英文别名: (2S,3S)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-ol
• 化学式: C₁₃H₁₈N₂O
• 分子量: 218.299
• InChiKey: CKDDUULIRPQPSS-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 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：
  36.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cis-2-(3-pyridylmethyl)-3-quinuclidinol 在 四(三苯基膦)钯 、 lithium hydroxide monohydrate 、 偶氮二甲酸二异丙酯 、 potassium tert-butylate 、 sodium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 反应 38.0h， 生成 trans-5-[5-[2-(3-pyridylmethyl)quinuclidin-3-yl]oxypyrazin-2-yl]-1H-indole
  参考文献：
  名称：

  作为潜在镇咳剂的新型 α7 烟碱型乙酰胆碱受体调节剂

  摘要：

  设计了一系列新的 α7 烟碱型乙酰胆碱受体 (nAChR) 调节剂，并评估了其在体内化学诱发咳嗽的豚鼠模型中的镇咳活性。所有测试剂量（9.5、3 和 1 mg/kg）的化合物16显着（p < 0.01）减少咳嗽的累积次数，并显示与阳性对照（30 mg/kg 的可待因）相似的结果。在三种不同的给药途径（腹膜内、口服和吸入）中，化合物16在吸入剂量低至 0.4 mg/kg 时对豚鼠产生显着的镇咳作用 ( p < 0.05)。α7 nAChR 调节剂可为急性和慢性咳嗽患者提供一种新型的非麻醉性治疗方法。

  DOI：

  10.1016/j.bmcl.2022.129067
• 作为产物：
  描述：

  2-(吡啶-3-基甲基)奎宁环-3-酮 在 aluminum isopropoxide 作用下， 以 异丙醇 为溶剂， 以79.2 %的产率得到cis-2-(3-pyridylmethyl)-3-quinuclidinol
  参考文献：
  名称：

  作为潜在镇咳剂的新型 α7 烟碱型乙酰胆碱受体调节剂

  摘要：

  设计了一系列新的 α7 烟碱型乙酰胆碱受体 (nAChR) 调节剂，并评估了其在体内化学诱发咳嗽的豚鼠模型中的镇咳活性。所有测试剂量（9.5、3 和 1 mg/kg）的化合物16显着（p < 0.01）减少咳嗽的累积次数，并显示与阳性对照（30 mg/kg 的可待因）相似的结果。在三种不同的给药途径（腹膜内、口服和吸入）中，化合物16在吸入剂量低至 0.4 mg/kg 时对豚鼠产生显着的镇咳作用 ( p < 0.05)。α7 nAChR 调节剂可为急性和慢性咳嗽患者提供一种新型的非麻醉性治疗方法。

  DOI：

  10.1016/j.bmcl.2022.129067

文献信息

• 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。
• Method for producing optically active quinuclidinols having one or more substituted groups at the 2-position
  申请人：Katayama Takeaki

  公开号：US20080081911A1

  公开（公告）日：2008-04-03

  The invention provides a method for producing optically active 3-quinuclidinols having one or more substituted groups at the 2-position; wherein 3-quinuclidinones having one or more substituted groups at the 2-position are reacted with compounds providing hydrogen in the presence of a certain metal complex.

  本发明提供了一种制备在2位具有一个或多个取代基的光学活性3-喹诺啉醇的方法；其中，在特定金属配合物的存在下，将在2位具有一个或多个取代基的3-喹诺酮与提供氢的化合物反应。
• 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。
• 3-SUBSTITUTED-2(ARYLALKYL)-1-AZABICYCLOALKANES AND METHODS OF USE THEREOF
  申请人：Mazurov Anatoly A.

  公开号：US20110071187A1

  公开（公告）日：2011-03-24

  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一个5-或6-成员环的杂芳基，优选为3-吡啶基和5-嘧啶基团，而烷基通常是C1-4烷基。在1-氮杂双环烷的3位取代基是含有羰基的基团，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包括中枢神经系统(CNS)疾病在内的疾病和障碍的方法，这些疾病和障碍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，例如与肿瘤生长相关的新生血管化。