2-benzylquinuclidin-3-amine | 40615-00-7

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-benzylquinuclidin-3-amine
• 英文别名: trans 2-benzylquinuclidin-3-amine；2-benzyl-1-azabicyclo[2.2.2]octan-3-amine
• CAS: 40615-00-7
• 化学式: C₁₄H₂₀N₂
• 分子量: 216.326
• InChiKey: XPPMDYURPXXBHC-UHFFFAOYSA-N

物化性质

• 沸点：
  327.7±25.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-benzylquinuclidin-3-amine 、 2-碘苯甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以90%的产率得到
  参考文献：
  名称：

  Overcoming chloroquine resistance in malaria: Design, synthesis and structure–activity relationships of novel chemoreversal agents

  摘要：

  Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.058
• 作为产物：
  描述：

  (Z)-2-benzylidene-1-azabicyclo[2.2.2]octan-3-one 在 palladium on activated carbon 、 氢气 、 zinc(II) chloride 作用下， 以 甲醇 、 乙醚 为溶剂， 20.0 ℃ 、206.85 kPa 条件下， 反应 7.5h， 生成 2-benzylquinuclidin-3-amine
  参考文献：
  名称：

  Overcoming chloroquine resistance in malaria: Design, synthesis and structure–activity relationships of novel chemoreversal agents

  摘要：

  Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.058

文献信息

• Substituted azabicyclic moieties for the treatment of disease
  申请人：——

  公开号：US20030055043A1

  公开（公告）日：2003-03-20

  The invention provides compounds of Formula I: 1 wherein m 1 is 0 or 1; m 2 is 1 or 2; R 1 is —H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, or phenyl; R 2 is —H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, or phenyl, provided that when m 1 is 1 at least one of R 1 and R 2 is —H; or a pharmaceutically acceptable salt, pharmaceutical composition, a pure enantiomer or racemic mixture thereof. The invention also provides a method for treating a disease or condition in a mammal, wherein the &agr;7 nicotinic acetylcholine receptor is implicated and for treating diseases where there is a sensory-gating deficit in a mammal comprising administering to a mammal a therapeutically effective amount of a compound of Formula I. These compounds may be in the form of pharmaceutical salts or compositions, and may be in pure enantiomeric form or may be racemic mixtures.

  该发明提供了Formula I的化合物：其中m1为0或1；m2为1或2；R1为—H、烷基、卤代烷基、取代烷基、环烷基或苯基；R2为—H、烷基、卤代烷基、取代烷基、环烷基或苯基，但当m1为1时，至少一个R1和R2中有一个为—H；或其药学上可接受的盐、药物组合物、纯对映体或混合物。该发明还提供了一种治疗哺乳动物疾病或症状的方法，其中α7烟碱乙酰胆碱受体起作用，并用于治疗哺乳动物中存在感觉门控缺陷的疾病，包括向哺乳动物施用Formula I化合物的治疗有效量。这些化合物可以是药物盐或组合物的形式，并且可以是纯对映体形式或混合物。
• [EN] PROCESS FOR PREPARATION OF 1-(2S,3S)-2-BENZHYDR YL-N-(5-TERT-BUTYL-2-METHOXYBENZYL)QUINUCLIDIN-3-AMINE<br/>[FR] PROCEDE DE PREPARATION DE 1-(2S,3S)-2-BENZHYDRYL-N-(5-TERT-BUTYL-2-METHOXYBENZYL)QUINUCLIDINE-3-AMINE
  申请人：PFIZER PROD INC

  公开号：WO2005075473A1

  公开（公告）日：2005-08-18

  This invention relates to an improved process for the preparation of (2S,3S)-­ 2-benzhydryl-N-(5-tent-butyl-2-methoxybenzyl)quinuclidin-3-amine, (hereinafter 'compound of Formula I') and its pharmaceutically acceptable salts. In particular, the invention is directed to an improved synthesis of the monohydrate citrate salt of the compound of Formula (la).

  本发明涉及一种改进的工艺，用于制备(2S,3S)-2-苯甲基-N-(5-叔丁基-2-甲氧基苯基)喹诺啉-3-胺（以下简称“公式I化合物”）及其药学上可接受的盐。特别地，本发明针对公式(la)化合物的单水合柠檬酸盐的合成进行了改进。
• [EN] SUBSTITUTED AZABICYCLIC MOIETIES FOR THE TREATMENT OF DISEASE (NICOTINIC ACETHYLCHOLINE RECEPTOR ANTAGONISTS)<br/>[FR] FRACTIONS AZABICYCLIQUES SUBSTITUEES POUR LE TRAITEMENT DE MALADIES (ANTAGONISTES DU RECEPTEUR D'ACETHYLCHOLINE NICOTINIQUE)
  申请人：UPJOHN CO

  公开号：WO2002085901A1

  公开（公告）日：2002-10-31

  The invention provides compounds of Formula (I): (F) Formula (I) wherein m1 is 0 or 1; m2 is 1 or 2; R¿1? is-H, alkyl, halogenated alkyl, substituted alkyl, cycloakyl, or phenyl; R2 is -H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, or phenyl, provided that when m?1¿ is 1 at least one of R¿1? and R2 is -H; or a pharmaceutically acceptable salt, pharmaceutical composition, a pure enantiomer or racemic mixture thereof. The invention also provides a method for treating a disease or condition in a mammal, wherein the ≡7 nicotinic acetylcholine receptor is implicated and for treating diseases where there is a sensory-gating deficit in a mammal comprising administering to a mammal a therapeutically effective amount of a compound of Formula (I). These compounds may be in the form of phamaceutical salts or compositions, and may be in pure enantiomeric form or may be racemic mixtures.

  本发明提供了式(I)的化合物：（F）式（I），其中m1为0或1；m2为1或2；R1为-H，烷基，卤代烷基，取代烷基，环烷基或苯基；R2为-H，烷基，卤代烷基，取代烷基，环烷基或苯基，但当m1为1时，R1和R2中至少有一个为-H；或其药学上可接受的盐，制药组合物，其纯对映体或外消旋混合物。本发明还提供了一种用于治疗哺乳动物中涉及到≡7尼古丁乙酰胆碱受体的疾病或状况的方法，并用于治疗哺乳动物中存在感觉门控缺陷的疾病，包括向哺乳动物施用式(I)化合物的治疗有效量。这些化合物可以是制药盐或组合物的形式，并且可以是纯对映体形式或外消旋混合物。
• SUBSTITUTED AZABICYCLIC MOIETIES FOR THE TREATMENT OF DISEASE (NICOTINIC ACETHYLCHOLINE RECEPTOR ANTAGONISTS)
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP1389208A1

  公开（公告）日：2004-02-18
• SUBSTITUTED AZABICYCLIC MOIETIES FOR THE TREATMENT OF DISEASE (NICOTINIC ACETHYLCHOLINE RECEPTOR AGONISTS)
  申请人：Pharmacia & Upjohn Company LLC

  公开号：EP1389208B1

  公开（公告）日：2005-12-28