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 Ratti & 11 others Kevin D. Read, Maja Roscic, Ilaria Sartori, Simone Spada, Giovanna Tedesco, Luca Tarsi, Silvia Terreni, Filippo Visentini, Alessandro Zocchi, Laura Zonzini, Romano Di Fabio

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    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., ... 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
    Micheli, Fabrizio ; Cavanni, Paolo ; Andreotti, Daniele ; Arban, Roberto ; Benedetti, Roberto ; Bertani, Barbara ; Bettati, Michela ; Bettelini, Letizia ; Bonanomi, Giorgio ; Braggio, Simone ; Carletti, Renzo ; Checchia, Anna ; Corsi, Mauro ; Fazzolari, Elettra ; Fontana, Stefano ; Marchioro, Carla ; Merlo-Pich, Emilio ; Negri, Michele ; Oliosi, Beatrice ; Ratti, Emiliangelo ; Read, Kevin D. ; Roscic, Maja ; Sartori, Ilaria ; Spada, Simone ; Tedesco, Giovanna ; Tarsi, Luca ; Terreni, Silvia ; Visentini, Filippo ; Zocchi, Alessandro ; Zonzini, Laura ; Di Fabio, Romano. / 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane : a new potent and selective triple reuptake inhibitor. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 13. pp. 4989-5001.
    @article{b1476fe91d2f4ec4a1d0c14b60720aae,
    title = "6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: a new potent and selective triple reuptake inhibitor",
    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.",
    author = "Fabrizio Micheli and Paolo Cavanni and Daniele Andreotti and Roberto Arban and Roberto Benedetti and Barbara Bertani and Michela Bettati and Letizia Bettelini and Giorgio Bonanomi and Simone Braggio and Renzo Carletti and Anna Checchia and Mauro Corsi and Elettra Fazzolari and Stefano Fontana and Carla Marchioro and Emilio Merlo-Pich and Michele Negri and Beatrice Oliosi and Emiliangelo Ratti and Read, {Kevin D.} and Maja Roscic and Ilaria Sartori and Simone Spada and Giovanna Tedesco and Luca Tarsi and Silvia Terreni and Filippo Visentini and Alessandro Zocchi and Laura Zonzini and {Di Fabio}, Romano",
    year = "2010",
    month = "7",
    day = "8",
    doi = "10.1021/jm100481d",
    language = "English",
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    pages = "4989--5001",
    journal = "Journal of Medicinal Chemistry",
    issn = "0022-2623",
    publisher = "American Chemical Society",
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    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, Ratti, E, Read, KD, Roscic, M, Sartori, I, Spada, S, Tedesco, G, Tarsi, L, Terreni, S, Visentini, F, Zocchi, A, Zonzini, L & 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, vol. 53, no. 13, pp. 4989-5001. https://doi.org/10.1021/jm100481d

    6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane : a new potent and selective triple reuptake inhibitor. / Micheli, Fabrizio; Cavanni, Paolo; Andreotti, Daniele; Arban, Roberto; Benedetti, Roberto; Bertani, Barbara; Bettati, Michela; Bettelini, Letizia; Bonanomi, Giorgio; Braggio, Simone; Carletti, Renzo; Checchia, Anna; Corsi, Mauro; Fazzolari, Elettra; Fontana, Stefano; Marchioro, Carla; Merlo-Pich, Emilio; Negri, Michele; Oliosi, Beatrice; Ratti, Emiliangelo; Read, Kevin D.; Roscic, Maja; Sartori, Ilaria; Spada, Simone; Tedesco, Giovanna; Tarsi, Luca; Terreni, Silvia; Visentini, Filippo; Zocchi, Alessandro; Zonzini, Laura; Di Fabio, Romano.

    In: Journal of Medicinal Chemistry, Vol. 53, No. 13, 08.07.2010, p. 4989-5001.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane

    T2 - a new potent and selective triple reuptake inhibitor

    AU - Micheli, Fabrizio

    AU - Cavanni, Paolo

    AU - Andreotti, Daniele

    AU - Arban, Roberto

    AU - Benedetti, Roberto

    AU - Bertani, Barbara

    AU - Bettati, Michela

    AU - Bettelini, Letizia

    AU - Bonanomi, Giorgio

    AU - Braggio, Simone

    AU - Carletti, Renzo

    AU - Checchia, Anna

    AU - Corsi, Mauro

    AU - Fazzolari, Elettra

    AU - Fontana, Stefano

    AU - Marchioro, Carla

    AU - Merlo-Pich, Emilio

    AU - Negri, Michele

    AU - Oliosi, Beatrice

    AU - Ratti, Emiliangelo

    AU - Read, Kevin D.

    AU - Roscic, Maja

    AU - Sartori, Ilaria

    AU - Spada, Simone

    AU - Tedesco, Giovanna

    AU - Tarsi, Luca

    AU - Terreni, Silvia

    AU - Visentini, Filippo

    AU - Zocchi, Alessandro

    AU - Zonzini, Laura

    AU - Di Fabio, Romano

    PY - 2010/7/8

    Y1 - 2010/7/8

    N2 - 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.

    AB - 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.

    U2 - 10.1021/jm100481d

    DO - 10.1021/jm100481d

    M3 - Article

    VL - 53

    SP - 4989

    EP - 5001

    JO - Journal of Medicinal Chemistry

    JF - Journal of Medicinal Chemistry

    SN - 0022-2623

    IS - 13

    ER -