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

ID: ALA4311986

Journal: Eur J Med Chem

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

Authors: Wróbel MZ, Chodkowski A, Herold F, Marciniak M, Dawidowski M, Siwek A, Starowicz G, Stachowicz K, Szewczyk B, Nowak G, Belka M, Bączek T, Satała G, Bojarski AJ, Turło J.

Abstract: A series of novel 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesised and evaluated for their 5-HT_1A/D₂/5-HT_2A/5-HT₆/5-HT₇ receptor affinity and serotonin reuptake inhibition. Most of the evaluated compounds displayed high affinities for 5-HT_1A receptors (e.g., 4cK_i = 2.3 nM, 4lK_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 MW005 (agonist of the pre- and postsynaptic 5-HT_1A receptor) exhibited promising affinities for the 5-HT_1A/SERT/D₂/5-HT₆/5-HT₇ receptors and showed an antidepressant-like activity in the FST model.

CiteXplore: 31586817

DOI: 10.1016/j.ejmech.2019.111736

Patent ID: ┄