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, Ferdinando Fiorino.

Journal Name: Medicinal Chemistry

Volume 16 , Issue 4 , 2020

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Graphical 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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Article Details

Year: 2020
Page: [517 - 530]
Pages: 14
DOI: 10.2174/1573406415666190613153220
Price: $65

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