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

doi:10.1021/jm100481d

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

Research output: Contribution to journal › Article › peer-review

58 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 language	English
Pages (from-to)	4989-5001
Number of pages	13
Journal	Journal of Medicinal Chemistry
Volume	53
Issue number	13
DOIs	https://doi.org/10.1021/jm100481d
Publication status	Published - 8 Jul 2010

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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., ... 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

@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 = jul,

day = "8",

doi = "10.1021/jm100481d",

language = "English",

volume = "53",

pages = "4989--5001",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "13",

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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

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

C2 - 20527970

SN - 0022-2623

VL - 53

SP - 4989

EP - 5001

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 13

ER -

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

Abstract

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