Novel Mannich Bases, 5‐Arylimidazolidine‐2, 4‐dione Derivatives with Dual 5‐HT1A Receptor and Serotonin Transporter Affinity. Issue 2 (3rd January 2013)

• Record Type: Journal Article
• Authors: Czopek, Anna; Kołaczkowski, Marcin; Bucki, Adam; Byrtus, Hanna; Pawłowski, Maciej; Siwek, Agata; Bojarski, Andrzej J.; Bednarski, Marek; Wróbel, Dagmara; Wesołowska, Anna
• Is Part Of: Archiv der Pharmazie. Volume 346:Issue 2(2013:Feb.)
• Page Start: 98
• Page End: 109
• Publication Date: 2013-01-03
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201200378
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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, α₁ and SERT affinity. Two selected compounds (<bold>5</bold>, <bold>9</bold>) 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 α₁ 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 <bold>5</bold> (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.</p> </abstract>