Discovery of Novel Indolealkylpiperazine Derivatives as Potent 5-HT 1A Receptor Agonists for the Potential Future Treatment of Depression

Depression is a severe psychiatric disorder that affects over 100 million people worldwide. 5-HT receptor agonists have been implicated in the treatment of a variety of central nervous system diseases, especially depression. In this study, based on , a selective potent 5-HT R agonist discovered via dynamic pharmacophore-based virtual screening, a series of indolealkylpiperazine derivatives with a benzamide moiety were designed and synthesized by the modification of the amide tail group as well as indole head group of . Among all tested compounds, displayed potent agonistic activity towards 5-HT R with an EC value of 1.01 nM. Molecular docking studies were performed to disclose the mechanism of its potent agonistic activity and high selectivity. Finally, the activation model of 5-HT R induced by was proposed.