1-Heteroaryl-6-(3,4-dichlorophenyl)-3-azabicyclo[4.1.0]heptane: further insights into a class of triple re-uptake inhibitors

Fabrizio Micheli; Paolo Cavanni; Michela Bettati; Giorgio Bonanomi; Romano Di Fabio; Elettra Fazzolari; Carla Marchioro; Maja Roscic; Luca Tarsi; Filippo Visentini; Laura Zonzini; Angela Worby

doi:10.1016/j.bmc.2011.04.032

1-Heteroaryl-6-(3,4-dichlorophenyl)-3-azabicyclo[4.1.0]heptane: further insights into a class of triple re-uptake inhibitors

Bioorg Med Chem. 2011 Jun 1;19(11):3451-61. doi: 10.1016/j.bmc.2011.04.032. Epub 2011 Apr 22.

Authors

Fabrizio Micheli¹, Paolo Cavanni, Michela Bettati, Giorgio Bonanomi, Romano Di Fabio, Elettra Fazzolari, Carla Marchioro, Maja Roscic, Luca Tarsi, Filippo Visentini, Laura Zonzini, Angela Worby

Affiliation

¹ GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. fabrizio.micheli@aptuit.com

PMID: 21550808
DOI: 10.1016/j.bmc.2011.04.032

Abstract

Further exploration around the recently disclosed potent triple re-uptake inhibitor 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane led to the identification of a new series of potent triple re-uptake inhibitors endowed with good developability characteristics. The insertion of a further aryl moiety into the template allowed the 'titration' of the SERT/NET/DAT ratio leading to the identification of further tools in this important area.

MeSH terms

Adrenergic Uptake Inhibitors / chemical synthesis
Adrenergic Uptake Inhibitors / chemistry*
Adrenergic Uptake Inhibitors / pharmacology
Aza Compounds / chemistry
Bridged Bicyclo Compounds / chemistry
Dopamine Plasma Membrane Transport Proteins / chemistry
Dopamine Plasma Membrane Transport Proteins / metabolism
Dopamine Uptake Inhibitors / chemical synthesis
Dopamine Uptake Inhibitors / chemistry*
Dopamine Uptake Inhibitors / pharmacology
Heptanes / chemical synthesis
Heptanes / chemistry*
Heptanes / pharmacology
Humans
Norepinephrine Plasma Membrane Transport Proteins / chemistry
Norepinephrine Plasma Membrane Transport Proteins / metabolism
Protein Binding
Selective Serotonin Reuptake Inhibitors / chemical synthesis
Selective Serotonin Reuptake Inhibitors / chemistry*
Selective Serotonin Reuptake Inhibitors / pharmacology
Serotonin Plasma Membrane Transport Proteins / chemistry
Serotonin Plasma Membrane Transport Proteins / metabolism
Structure-Activity Relationship

Substances

Adrenergic Uptake Inhibitors
Aza Compounds
Bridged Bicyclo Compounds
Dopamine Plasma Membrane Transport Proteins
Dopamine Uptake Inhibitors
Heptanes
Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors