2-benzhydrylquinuclidin-3-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-benzhydrylquinuclidin-3-amine
• 英文别名: (2S,3R)-2-benzhydryl-1-azabicyclo[2.2.2]octan-3-amine
• 化学式: C₂₀H₂₄N₂
• 分子量: 292.424
• InChiKey: MECDCHFRZHLREI-UXHICEINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (Z)-2-benzylidene-1-azabicyclo[2.2.2]octan-3-one 在 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 苯 为溶剂， 反应 1.5h， 生成 (-)-(2S,3S)-cis-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine 、 2-benzhydrylquinuclidin-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

• [EN] PROCESS FOR THE PREPARATION OF (S,S)-CIS-2-BENZHYDRYL-3-BENZYLAMINOQUINUCLIDINE<br/>[FR] PROCEDE DE PREPARATION DE (S,S)-CIS-2-BENZHYDRYL-3-BENZYLAMINOQUINUCLIDINE
  申请人：PFIZER PROD INC

  公开号：WO2004035575A1

  公开（公告）日：2004-04-29

  A process for preparing (S,S)-cis-2-benzhydryl-3-benzylaminoquinuclidine. The process includes the steps of contacting a compound containing a mixture of R- and S-isomers and having Formula (I), with an effective amount of a chiral organic acid in the presence of an organic solvent and an effective amount of an organic carboxylic acid for converting the R-isomer into an acid salt of the S isomer, wherein the organic solvent is capable of solubilizing the compound containing the mixture of R- and S-isomers, while precipitating the acid salt and the organic carboxylic acid is different from the chiral organic acid; neutralizing the acid salt with a base to provide an S-isomer of a chiral ketone of Formula (II), and reacting the chiral ketone with an organic amine in the presence of a Lewis acid to provide the corresponding imine and reducing the imine.

  一种制备(S,S)-顺式-2-苄基-3-苄基氨基喹啉的方法。该方法包括以下步骤：将含有R-和S-异构体混合物且具有化学式(I)的化合物与有效量的手性有机酸在有机溶剂存在下接触，并加入有效量的有机羧酸以将R-异构体转化为S异构体的酸盐，其中有机溶剂能溶解含有R-和S-异构体混合物的化合物，同时沉淀出酸盐，有机羧酸与手性有机酸不同；用碱中和酸盐以提供化学式(II)的手性酮的S-异构体，并在路易斯酸存在下将手性酮与有机胺反应以提供相应的亚胺，然后还原亚胺。
• Process for the preparation of (S,S)-cis-2-benzhydryl-3-benzylaminoquinuclidine
  申请人：PFIZER INC.

  公开号：US20040116704A1

  公开（公告）日：2004-06-17

  A process for preparing (S,S)-cis-2-benzhydryl-3-benzylaminoquinuclidine. The process includes the steps of contacting a compound containing a mixture of R- and S-isomers and having the formula 1 with an effective amount of a chiral organic acid in the presence of an organic solvent and an effective amount of an organic carboxylic acid for converting the R-isomer into an acid salt of the S isomer, wherein the organic solvent is capable of solubilizing the compound containing the mixture of R- and S-isomers, while precipitating the acid salt and the organic carboxylic acid is different from the chiral organic acid; neutralizing the acid salt with a base to provide an S-isomer of a chiral ketone of the formula 2 reacting the chiral ketone with an organic amine in the presence of a Lewis acid to provide the corresponding imine and reducing the imine.

  一种制备(S,S)-顺式-2-苯甲基-3-苄基氨基喹啉的方法。该方法包括以下步骤：将含有R-和S-异构体混合物且具有公式1的化合物与手性有机酸的有效量在有机溶剂和有机羧酸的有效量的存在下接触，以将R-异构体转化为S-异构体的酸盐，其中有机溶剂能够溶解含有R-和S-异构体混合物的化合物，同时沉淀酸盐，有机羧酸不同于手性有机酸；用碱中和酸盐以提供公式2的手性酮的S-异构体；在路易斯酸的存在下，将手性酮与有机胺反应以提供相应的亚胺，并还原亚胺。
• QUINUCLIDINE THERAPEUTIC AGENTS
  申请人：PFIZER INC.

  公开号：EP0409931A1

  公开（公告）日：1991-01-30
• PROCESS FOR THE PREPARATION OF (S,S)-CIS-2-BENZHYDRYL-3-BENZYLAMINOQUINUCLIDINE
  申请人：Pfizer Products Inc.

  公开号：EP1551833A1

  公开（公告）日：2005-07-13
• US5162339A
  申请人：——

  公开号：US5162339A

  公开（公告）日：1992-11-10