6-(3,4-Dichlorophenyl)-1-[(Methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: A New Potent and Selective Triple Reuptake Inhibitor
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- 作者：Fabrizio Micheli ; Paolo Cavanni ; Daniele Andreotti ; Roberto Arban ; Roberto Benedetti ; Barbara Bertani ; Michela Bettati ; Letizia Bettelini ; Giorgio Bonanomi ; Simone Braggio ; Renzo Carletti ; Anna Checch
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：July 8, 2010
- 年：2010
- 卷：53
- 期：13
- 页码：4989-5001
- 全文大小：1065K
- 年卷期：v.53,no.13(July 8, 2010)
- ISSN：1520-4804
文摘
A pharmacophore model for triple reuptake inhibitors and the new class of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes were recently reported. Further investigation in this area led to the identification of a new series of potent and selective triple reuptake inhibitors endowed with good developability characteristics. Excellent bioavailability and brain penetration are associated with this series of 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptanes together with high in vitro potency and selectivity at SERT, NET, and DAT. In vivo microdialysis experiments in different animal models and receptor occupancy studies in rat confirmed that derivative 17 showed an appropriate profile to guarantee further progression of the compound.