cis-2-benzyl-3-<(3,5-dimethylbenzyl)oxy>-1-azabicyclo<2.2.2>octane

• 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: cis-2-benzyl-3-<(3,5-dimethylbenzyl)oxy>-1-azabicyclo<2.2.2>octane
• 英文别名: (2S,3S)-2-benzyl-3-[(3,5-dimethylphenyl)methoxy]-1-azabicyclo[2.2.2]octane
• 化学式: C₂₃H₂₉NO
• 分子量: 335.489
• InChiKey: XSUZGCYNKOVZIW-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-benzylquinuclidin-3-one 在 双(三甲基硅烷基)氨基钾 、 三乙基硼氢化锂 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 4.0h， 生成 cis-2-benzyl-3-<(3,5-dimethylbenzyl)oxy>-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

文献信息

• 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.