Synthesis and structure–activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with a heterocyclic ring constraint

The design, synthesis and SAR of a series of heterocyclic ring-constrained norepinephrine reuptake inhibitors are described. As racemates, the best compounds compare favorably with atomoxetine (IC50’s < 10 nM) in potency at the transporter.

Graphical abstractA series of heterocyclic ring-constrained norepinephrine reuptake inhibitors have activities as racemates equivalent to atomoxetine (IC50’s < 10 nM).Figure optionsDownload full-size imageDownload as PowerPoint slide