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Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1.

Abstract：

:A series of 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives was synthesized and their biological activity was evaluated. The chemical structures of the newly prepared compounds were confirmed by (1)H NMR, (13)C NMR and ESI-HRMS spectra data. All tested compounds proved to be potent 5-HT1A receptor and serotonin transporter protein (SERT) ligands. Among them, compounds 15, 18, 19 and 30 showed significant affinity for 5-HT1A and SERT. Computer docking simulations carried out for compounds 15, 31 and 32 to models of 5-HT1A receptor and SERT confirm the results of biological tests. Due to high affinity for the 5-HT1A receptor and moderate affinity for SERT, compounds 31, 32, 35, and 37 were evaluated for their affinity for D2L, 5-HT6, 5-HT7 and 5-HT2A receptors. In vivo tests, in turn, resulted in determining the functional activity of compounds 15, 18, 19 and 30 to the 5-HT1A receptor. The results of these tests indicate that all of the ligands possess properties characteristic of 5-HT1A receptor agonists.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Wróbel MZ,Chodkowski A,Herold F,Gomółka A,Kleps J,Mazurek AP,Pluciński F,Mazurek A,Nowak G,Siwek A,Stachowicz K,Sławińska A,Wolak M,Szewczyk B,Satała G,Bojarski AJ,Turło J

doi

10.1016/j.ejmech.2013.02.033

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

484-500

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(13)00140-2

journal_volume

63

pub_type

杂志文章

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