2-Benzylidene-1-azabicyclo[2.2.2]octan-3-ol | 112611-41-3

• 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: 2-Benzylidene-1-azabicyclo[2.2.2]octan-3-ol
• CAS: 112611-41-3
• 化学式: C₁₄H₁₇NO
• 分子量: 215.295
• InChiKey: XCJLSGXSDDYLKZ-UHFFFAOYSA-N

物化性质

• 沸点：
  391.6±31.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5-二甲基溴苄 、 2-Benzylidene-1-azabicyclo[2.2.2]octan-3-ol 在 18-冠醚-6 、 双(三甲基硅烷基)氨基钾 作用下， 生成 2-Benzylidene-3-[(3,5-dimethylphenyl)methoxy]-1-azabicyclo[2.2.2]octane
  参考文献：
  名称：

  Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists

  摘要：

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.

  DOI：

  10.1021/jm00024a007
• 作为产物：
  描述：

  (Z)-2-benzylidene-1-azabicyclo[2.2.2]octan-3-one 在 盐酸 、 氢氧化钾 、 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 2-Benzylidene-1-azabicyclo[2.2.2]octan-3-ol
  参考文献：
  名称：

  Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists

  摘要：

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.

  DOI：

  10.1021/jm00024a007

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.

  本发明提供了式I的化合物：1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、制剂、纯对映体或混合物。本发明还提供了一种用于治疗哺乳动物中涉及α7烟碱性乙酰胆碱受体的疾病或症状的方法，以及用于治疗哺乳动物中存在感觉门控缺陷的疾病的方法，包括向哺乳动物投与式I化合物的治疗有效量。这些化合物可以以药物盐或制剂的形式存在，并且可以是纯对映体形式或可以是混合物。
• Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists
  作者：Christopher J. Swain、Eileen M. Sewart、Margaret A. Cascieri、Tung M. Fong、Richard Herbert、D Euan MacIntyre、Kevin J. Merchant、Simon N. Owen、Andrew P. Owens

  DOI：10.1021/jm00024a007

  日期：1995.11

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.