6-(3,4-Dichlorophenyl)-1-[(Methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: A New Potent and Selective Triple Reuptake Inhibitor

• DOI: 10.1021/jm100481d
• Publication Date: 2010-06-09T13:58:16Z
• Authors: 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
• Keywords: Male; Models, Molecular; monoamine transporters; Serotonin; Magnetic Resonance Spectroscopy; Dopamine; Microdialysis; 610; CNS; depression; triple reuptake inhibitors; TRUI; monoamine transporters; 01 natural sciences; Mass Spectrometry; Heptanes; Rats, Sprague-Dawley; Mice; Norepinephrine; Structure-Activity Relationship; triple reuptake inhibitors; Animals; Humans; Neurotransmitter Uptake Inhibitors; Depressive Disorder; TRUI; Brain; 540; Antidepressive Agents; Rats; 3. Good health; 0104 chemical sciences; depression; CNS; Azabicyclo Compounds

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 identification a series potent selective endowed with good developability characteristics. Excellent bioavailability brain penetration are associated 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptanes together high vitro potency selectivity at SERT, NET, DAT. In vivo microdialysis experiments different animal models receptor occupancy studies rat confirmed that derivative 17 showed an appropriate profile guarantee further progression compound.