1,1-dimethylethyl (1S,5S,6S/1R,5R,6R)-1-(3,4-dichlorophenyl)-6-[(ethyloxy)methyl]-3-azabicyclo[3.1.0]hexane-3-carboxylate

• 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: 1,1-dimethylethyl (1S,5S,6S/1R,5R,6R)-1-(3,4-dichlorophenyl)-6-[(ethyloxy)methyl]-3-azabicyclo[3.1.0]hexane-3-carboxylate
• 英文别名: tert-butyl (1R,5R,6R)-1-(3,4-dichlorophenyl)-6-(ethoxymethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate
• 化学式: C₁₉H₂₅Cl₂NO₃
• 分子量: 386.318
• InChiKey: ZNJLQLXJMWREEP-LPMFXHHGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl (1S,5S,6S/1R,5R,6R)-1-(3,4-dichlorophenyl)-6-[(ethyloxy)methyl]-3-azabicyclo[3.1.0]hexane-3-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 exo-1-(3,4-dichlorophenyl)-6-[(ethyloxy)methyl]-3-azabicyclo[3.1.0]hexane
  参考文献：
  名称：

  1-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes: A New Series of Potent and Selective Triple Reuptake Inhibitors

  摘要：

  The discovery of new highly potent and selective triple reuptake inhibitors is reported. The new classes of 1-(ary1)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes are described together with detailed SA R. Appropriate decoration of the scaffolds was achieved with the help of a triple reuptake inhibitor pharmacophore model detailed here. Selected derivatives showed good oral bioavailability ( > 30%) and brain penetration (B/B > 4) in rats associated with high in vitro potency and selectivity at SERT, NET, and DAT. Among these compounds, microdialysis and in vivo experiments confirm that derivative 15 has an appropriate developability profile to be considered for further progression.

  DOI：

  10.1021/jm901818u
• 作为产物：
  描述：

  1,1-dimethylethyl (1R,5R,6R/1S,5S,6S)-1-(3,4-dichlorophenyl)-6-(hydroxymethyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylate 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1,1-dimethylethyl (1S,5S,6S/1R,5R,6R)-1-(3,4-dichlorophenyl)-6-[(ethyloxy)methyl]-3-azabicyclo[3.1.0]hexane-3-carboxylate
  参考文献：
  名称：

  1-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes: A New Series of Potent and Selective Triple Reuptake Inhibitors

  摘要：

  The discovery of new highly potent and selective triple reuptake inhibitors is reported. The new classes of 1-(ary1)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes are described together with detailed SA R. Appropriate decoration of the scaffolds was achieved with the help of a triple reuptake inhibitor pharmacophore model detailed here. Selected derivatives showed good oral bioavailability ( > 30%) and brain penetration (B/B > 4) in rats associated with high in vitro potency and selectivity at SERT, NET, and DAT. Among these compounds, microdialysis and in vivo experiments confirm that derivative 15 has an appropriate developability profile to be considered for further progression.

  DOI：

  10.1021/jm901818u

文献信息

• WO2008/74716
  申请人：——

  公开号：——

  公开（公告）日：——
• 1-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes: A New Series of Potent and Selective Triple Reuptake Inhibitors
  作者：Fabrizio Micheli、Paolo Cavanni、Roberto Arban、Roberto Benedetti、Barbara Bertani、Michela Bettati、Letizia Bettelini、Giorgio Bonanomi、Simone Braggio、Anna Checchia、Silvia Davalli、Romano Di Fabio、Elettra Fazzolari、Stefano Fontana、Carla Marchioro、Doug Minick、Michele Negri、Beatrice Oliosi、Kevin D. Read、Ilaria Sartori、Giovanna Tedesco、Luca Tarsi、Silvia Terreni、Filippo Visentini、Alessandro Zocchi、Laura Zonzini

  DOI：10.1021/jm901818u

  日期：2010.3.25

  The discovery of new highly potent and selective triple reuptake inhibitors is reported. The new classes of 1-(ary1)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes are described together with detailed SA R. Appropriate decoration of the scaffolds was achieved with the help of a triple reuptake inhibitor pharmacophore model detailed here. Selected derivatives showed good oral bioavailability ( > 30%) and brain penetration (B/B > 4) in rats associated with high in vitro potency and selectivity at SERT, NET, and DAT. Among these compounds, microdialysis and in vivo experiments confirm that derivative 15 has an appropriate developability profile to be considered for further progression.