Novel Mannich Bases, 5‐Arylimidazolidine‐2,4‐dione Derivatives with Dual 5‐HT1A Receptor and Serotonin Transporter Affinity

doi:10.1002/ardp.201200378

Paper

Novel Mannich Bases, 5‐Arylimidazolidine‐2,4‐dione Derivatives with Dual 5‐HT1A Receptor and Serotonin Transporter Affinity

Published Feb 1, 2013 · A. Czopek, M. Kołaczkowski, Adam Bucki

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Abstract

A computer aided ligand design study of imidazolidine‐2,4‐dione derivatives was conducted in order to obtain compounds with dual 5‐HT1A 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‐HT1A, 5‐HT2A, α1 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‐HT1A partial agonism and 5‐HT2A 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 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.

In Vitro Study

Study Snapshot

5arylimidazolidine2,4dione derivatives with dual 5HT1A receptor and serotonin transporter affinity show potential for antidepressant and anxiolytic activity without affecting spontaneous locomotor activity.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Novel Mannich Bases, 5‐Arylimidazolidine‐2,4‐dione Derivatives with Dual 5‐HT1A Receptor and Serotonin Transporter Affinity

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Citations

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Imidazole-based derivatives show potential as serotonergic system modulators for treating depression, offering unique structural characteristics and diverse bioactivities.

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Serotonin receptors 5-HT1A and 5-HT7 are crucial for mood regulation, sleep, and appetite, but their functional interaction remains unidentified.

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