Design, synthesis, and pharmacological evaluation of phenoxy pyridyl derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists

Preclinical studies suggest that compounds with dual norepinephrine reuptake inhibitor (NRI) and 5-HT 1A partial agonist properties may provide an important new therapeutic approach to ADHD, depression, and anxiety. Reported herein is the discovery of a novel chemical series with a favorable NRI and 5-HT 1A partial agonist pharmacological profile as well as excellent selectivity for the norepinephrine transporter over the dopamine transporter.