New Serotoninergic Ligands Containing Indolic and Methyl Indolic Nuclei: Synthesis and In Vitro Pharmacological Evaluation
| Autor: | Irene Saccone, Vincenzo Santagada, Giuseppe Caliendo, José Brea, Angela Corvino, Beatrice Severino, Marián Castro, Elisa Perissutti, Francesco Frecentese, Flavia Giordano, Elisa Magli, Ferdinando Fiorino, Marian Isabel Loza |
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| Přispěvatelé: | Magli, E., Severino, B., Corvino, A., Perissutti, E., Frecentese, F., Saccone, I., Giordano, F., Castro, M., Brea, J., Loza, M. I., Santagada, V., Caliendo, G., Fiorino, F. |
| Rok vydání: | 2020 |
| Předmět: |
binding assay
chemistry.chemical_classification Indoles serotonin synthesis Ligand binding assay Arylpiperazine derivative Dopaminergic Ligands Serotonergic In vitro Structure-Activity Relationship Piperazine chemistry.chemical_compound chemistry Biochemistry indolic and methyl indolic nuclei Receptors Serotonin Biogenic amine Drug Discovery Humans Serotonin Receptor 5-HT1A 5-HT2A and 5-HT2C receptor ligand |
| Zdroj: | Medicinal Chemistry. 16:517-530 |
| ISSN: | 1573-4064 |
| Popis: | Background: Serotonin is an important biogenic amine and is implicated in wideranging physiological and physiopathological processes. Pharmacological manipulation of the serotoninergic system is believed to have a great therapeutic potential. Objectives: In order to identify selective ligands for 5-HT1A, 5-HT2A and 5-HT2C receptors two series of 4-substituted piperazine derivatives, bearing indolic or methyl indolic nuclei, were synthesized. Methods: All the compounds, synthesized by standard solution methods, were evaluated for 5- HT1A, 5-HT2A and 5-HT2C receptors. The highest affine and selective compounds have been evaluated also on dopaminergic (D1 and D2) and adrenergic (α1A and α2A) receptors. Results: Several of the newly synthesized molecules showed affinity in the nanomolar range for 5- HT1A, 5-HT2A and 5-HT2C receptors and moderate to no affinity for other relevant receptors (D1, D2, α1A and α2A). Conclusion: Compounds 7f and 10a showed a nanomolar affinity towards 5-HT1A with an in vitro pharmacologic profile compatible with antipsychotic drugs. |
| Databáze: | OpenAIRE |
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