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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

New Serotoninergic Ligands Containing Indolic and Methyl Indolic Nuclei: Synthesis and In Vitro Pharmacological Evaluation

Author(s): Elisa Magli, Beatrice Severino*, Angela Corvino, Elisa Perissutti, Francesco Frecentese, Irene Saccone, Flavia Giordano, Marián Castro, José Brea, María I. Loza, Vincenzo Santagada, Giuseppe Caliendo and Ferdinando Fiorino

Volume 16, Issue 4, 2020

Page: [517 - 530] Pages: 14

DOI: 10.2174/1573406415666190613153220

Price: $65

Abstract

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.

Keywords: Arylpiperazine derivatives, binding assay, indolic and methyl indolic nuclei, synthesis, serotonin, 5-HT1A, 5-HT2A and 5-HT2C receptor ligands.

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