Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1.
Eur J Med Chem
; 63: 484-500, 2013 May.
Article
in En
| MEDLINE
| ID: mdl-23524160
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrrolidines
/
Serotonin Agents
/
Antidepressive Agents
Type of study:
Prognostic_studies
Language:
En
Journal:
Eur J Med Chem
Year:
2013
Document type:
Article
Affiliation country:
Polonia