Effect of Modifications of the Alkylpiperazine Moiety of Trazodone on 5HT2A and α1 Receptor Binding Affinity

A series of triazolopyridine derivatives (compounds 2a − l) were synthesized in order to explore the effect of modifications of the alkylpiperazine moiety of trazodone (fragment A) on binding affinity for 5HT2A and α1 receptors. All of the synthesized compounds show a decrease of affinity for both 5...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1999-02, Vol.42 (3), p.336-345
Main Authors: Giannangeli, Marilena, Cazzolla, Nicola, Luparini, Maria Rita, Magnani, Maurizio, Mabilia, Massimo, Picconi, Giuseppe, Tomaselli, Mauro, Baiocchi, Leandro
Format: Article
Language:English
Subjects:
Biological and medical sciences
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Serotoninergic system
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Summary:A series of triazolopyridine derivatives (compounds 2a − l) were synthesized in order to explore the effect of modifications of the alkylpiperazine moiety of trazodone (fragment A) on binding affinity for 5HT2A and α1 receptors. All of the synthesized compounds show a decrease of affinity for both 5HT2A and α1 receptors, as compared to trazodone, with the exception of compounds 2b,c which bear a methyl group in an α position to the aliphatic nitrogen atom N1. These compounds showed a decrease of affinity only for the α1 receptor. The stereochemical influence of the piperazine moiety of compound 2c was also evaluated. Enantiomer ( S )-2c showed the most significant differences between 5HT2A and α1 receptor affinity (IC50 values) and among the corresponding functional properties (pA 2 values). Since ( S )-2c cannot generate the metabolite 4-(3-chlorophenyl)piperazine this product was selected for further pharmacological studies.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm970700n