Stereochemical optimization of ,2-substituted cycloalkylamines as norepinephrine reuptake inhibitors.

The norepinephrine transporter (NET), encoded by the SLC6A2 gene, is one of three key monoamine neurotransmitter transporters. Inhibition of NET-mediated reuptake of norepinephrine by monoamine reuptake inhibitors has been the main therapeutic strategy to treat disorders such as depression, ADHD and Parkinson's disease. Nevertheless, lack of efficacy as well as risk of adverse effects are still common for these treatments underscoring the necessity to improve drug discovery efforts for this target.

Development of subtype-selective covalent ligands for the adenosine A receptor by tuning the reactive group.

Signalling through the adenosine receptors (ARs), in particular through the adenosine A receptor (AAR), has been shown to play a role in a variety of pathological conditions, ranging from immune disorders to cancer. Covalent ligands for the AAR have the potential to irreversibly block the receptor, as well as inhibit all AAR-induced signalling pathways. This will allow a thorough investigation of the pathophysiological role of the receptor.