6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: a new potent and selective triple reuptake inhibitor

Fabrizio Micheli, Paolo Cavanni, Daniele Andreotti, Roberto Arban, Roberto Benedetti, Barbara Bertani, Michela Bettati, Letizia Bettelini, Giorgio Bonanomi, Simone Braggio, Renzo Carletti, Anna Checchia, Mauro Corsi, Elettra Fazzolari, Stefano Fontana, Carla Marchioro, Emilio Merlo-Pich, Michele Negri, Beatrice Oliosi, Emiliangelo RattiKevin D. Read, Maja Roscic, Ilaria Sartori, Simone Spada, Giovanna Tedesco, Luca Tarsi, Silvia Terreni, Filippo Visentini, Alessandro Zocchi, Laura Zonzini, Romano Di Fabio

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    Abstract

    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 further progression of the compound.

    Original languageEnglish
    Pages (from-to)4989-5001
    Number of pages13
    JournalJournal of Medicinal Chemistry
    Volume53
    Issue number13
    DOIs
    Publication statusPublished - 8 Jul 2010

    Cite this

    Micheli, F., Cavanni, P., Andreotti, D., Arban, R., Benedetti, R., Bertani, B., Bettati, M., Bettelini, L., Bonanomi, G., Braggio, S., Carletti, R., Checchia, A., Corsi, M., Fazzolari, E., Fontana, S., Marchioro, C., Merlo-Pich, E., Negri, M., Oliosi, B., ... Di Fabio, R. (2010). 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: a new potent and selective triple reuptake inhibitor. Journal of Medicinal Chemistry, 53(13), 4989-5001. https://doi.org/10.1021/jm100481d