Design, synthesis and pharmacological investigation of isoindoline derivatives as 5-HT/NE double reuptake inhibitors

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by ¹H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.