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

• Published in: Bioorganic & medicinal chemistry 2011-06, Vol.19 (11), p.3451-3461
• Main Authors: Micheli, Fabrizio, Cavanni, Paolo, Bettati, Michela, Bonanomi, Giorgio, Di Fabio, Romano, Fazzolari, Elettra, Marchioro, Carla, Roscic, Maja, Tarsi, Luca, Visentini, Filippo, Zonzini, Laura, Worby, Angela
• Format: Article
• Language: English
• Subjects: Adrenergic Uptake Inhibitors - chemical synthesis; Adrenergic Uptake Inhibitors - chemistry; Adrenergic Uptake Inhibitors - pharmacology; Aza Compounds - chemistry; Biological and medical sciences; Bridged Bicyclo Compounds - chemistry; Catecholaminergic system; chemical structure; DAT; 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; heptane; Heptanes - chemical synthesis; Heptanes - chemistry; Heptanes - pharmacology; Humans; Medical sciences; NET; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Norepinephrine Plasma Membrane Transport Proteins - chemistry; Norepinephrine Plasma Membrane Transport Proteins - metabolism; Pharmacology. Drug treatments; Pharmacophore; Protein Binding; Serotonin Plasma Membrane Transport Proteins - chemistry; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin Uptake Inhibitors - chemical synthesis; Serotonin Uptake Inhibitors - chemistry; Serotonin Uptake Inhibitors - pharmacology; Serotoninergic system; SERT; Structure-Activity Relationship; titration; Triple re-uptake inhibitors
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2011.04.032

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.