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.
New Serotoninergic Ligands Containing Indolic and Methyl Indolic Nuclei: Synthesis and In Vitro Pharmacological Evaluation / 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.. - In: MEDICINAL CHEMISTRY. - ISSN 1573-4064. - 16:4(2020), pp. 517-530. [10.2174/1573406415666190613153220]
New Serotoninergic Ligands Containing Indolic and Methyl Indolic Nuclei: Synthesis and In Vitro Pharmacological Evaluation
Magli E.;Severino B.;Corvino A.;Perissutti E.;Frecentese F.;Saccone I.;Giordano F.;Castro M.;Santagada V.;Caliendo G.;Fiorino F.
2020
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
