Premium
Novel Mannich Bases, 5‐Arylimidazolidine‐2,4‐dione Derivatives with Dual 5‐HT 1A Receptor and Serotonin Transporter Affinity
Author(s) -
Czopek Anna,
Kołaczkowski Marcin,
Bucki Adam,
Byrtus Hanna,
Pawłowski Maciej,
Siwek Agata,
Bojarski Andrzej J.,
Bednarski Marek,
Wróbel Dagmara,
Wesołowska Anna
Publication year - 2013
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200378
Subject(s) - chemistry , imidazolidine , serotonin transporter , 5 ht receptor , serotonin , anxiolytic , stereochemistry , moiety , receptor , behavioural despair test , pharmacology , transporter , antidepressant , biochemistry , endocrinology , biology , hippocampus , gene
A computer aided ligand design study of imidazolidine‐2,4‐dione derivatives was conducted in order to obtain compounds with dual 5‐HT 1A receptor and serotonin transporter (SERT) affinity. According to molecular modeling results, series of Mannich bases were chosen and synthesized. Investigated compounds were tested for 5‐HT 1A , 5‐HT 2A , α 1 and SERT affinity. Two selected compounds ( 5 , 9 ) were characterized in functional experiments and possessed a pharmacological profile which may enhance SERT blocking efficacy – 5‐HT 1A partial agonism and 5‐HT 2A antagonism in one molecule. Furthermore these compounds displayed satisfactory selectivity over adrenergic α 1 receptors. The most promising compounds, 5‐arylimidazolidine‐2,4‐dione derivatives with 4‐(3‐chlorophenyl)piperazinylmethyl moiety were tested for antidepressant and anxiolytic activity. In particular, compound 5 (5‐(2‐methoxyphenyl)‐3‐{1‐[4‐(3‐chlorophenyl)piperazin‐1‐yl]methyl}‐imidazolidine‐2,4‐dione), tested in the forced swim test in mice, exhibited a favorable antidepressant‐like profile without affecting spontaneous locomotor activity.