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

被引：25

作者：

Wrobel, Martyna Z. ^{[1
]}

Chodkowski, Andrzej ^{[1
]}

Herold, Franciszek ^{[1
]}

Marciniak, Monika ^{[1
]}

Dawidowski, Maciej ^{[1
]}

Siwek, Agata ^{[2
]}

Starowicz, Gabriela ^{[2
]}

Stachowicz, Katarzyna ^{[3
]}

Szewczyk, Bernadeta ^{[3
]}

Nowak, Gabriel ^{[2
,3
]}

Belka, Mariusz ^{[4
]}

Baczek, Tomasz ^{[4
]}

Satala, Grzegorz ^{[5
]}

Bojarski, Andrzej J. ^{[5
]}

Turlo, Jadwiga ^{[1
]}

机构：

[1] Med Univ Warsaw, Fac Pharm, Dept Drug Technol & Pharmaceut Biotechnol, 1 Banacha St, PL-02097 Warsaw, Poland

[2] Jagiellonian Univ, Fac Pharm, Dept Pharmacobiol, Med Coll, 9 Med St, PL-30688 Krakow, Poland

[3] Polish Acad Sci, Maj Inst Pharmacol, Dept Neurobiol, 12 Smetna St, PL-31343 Krakow, Poland

[4] Med Univ Gdansk, Dept Pharmaceut Chem, PL-80416 Gdansk, Poland

[5] Polish Acad Sci, Maj Inst Pharmacol, Dept Med Chem, 12 Smetna St, PL-31343 Krakow, Poland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 183卷

关键词：

Multitarget directed ligand; 5-HT1A agonists; 5-HT1A/SERT dual activity; Serotonin reuptake inhibitors; D-2 receptor ligands; Antidepressants; 5-HT1A RECEPTOR LIGANDS; DOPAMINE; SEROTONIN; METABOLISM; AGONISTS; SYSTEM; NEUROTRANSMISSION; PATHOPHYSIOLOGY; BREXPIPRAZOLE; SCHIZOPHRENIA;

D O I：

10.1016/j.ejmech.2019.111736

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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.

引用

页数：18

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