Abstract: A series of biarylbenzamidine analogs were synthesized and tested for their biological activities of inhibiting the reuptake of 5-HT. All of them were new compounds, and their structures were confirmed by ¹H NMR and HRMS. Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibition activity. Among the tested compounds, 5i, 4a and 5m exhibited potent inhibitory activity against 5-HT reuptake in vitro. It is a chance to find a better precursor of SSRIs (selective serotonin reuptake inhibitors) for further optimization of compounds.