Synthesis and biological evaluation of new multi-target 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with potential antidepressant effect

摘要

A series of novel 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesised and evaluated for their 5-HT1A/D-2/5-HT2A/5-HT6/5-HT7 receptor affinity and serotonin reuptake inhibition. Most of the evaluated compounds displayed high affinities for 5-HT1A receptors (e.g., 4c K-i = 23 nM, 41 K-i = 3.2 nM). The antidepressant activity of the selected compounds was screened in vivo using the forced swim test (FST). The results indicate that compound MWOOS (agonist of the pre- and postsynaptic 5-HT1A receptor) exhibited promising affinities for the 5-HT1A/SERT/D-2/5-HT6/5-HT7 receptors and showed an antidepressant-like activity in the FST model. (C) 2019 Elsevier Masson SAS. All rights reserved.