N’-Cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical for affinity to 5-HT1A receptors and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT2A and moderate to no affinity for other relevant receptors (5-HT1A, 5-HT2C, D1, D2, 1 and 2). N'-Cyano-N-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-picolinamidine (4l) with Ki = 0.000185 nM, was the most active and selective derivative for the 5-HT2A receptor compared to other serotoninergic, dopaminergic and adrenergic receptors.

New Potent 5-HT2A Receptor Ligands Containing a N'-Cyanopicolinamidine Nucleus: Synthesis and In Vitro Pharmacological Evaluation / Fiorino, Ferdinando; Severino, Beatrice; Magli, Elisa; Perissutti, Elisa; Frecentese, Francesco; A., Esposito; Incisivo, GIUSEPPINA MARIA; Ciano, Antonio; P., Massarelli; C., Nencini; Santagada, Vincenzo; Caliendo, Giuseppe. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 47:(2012), pp. 520-529. [10.1016/j.ejmech.2011.11.023]

New Potent 5-HT2A Receptor Ligands Containing a N'-Cyanopicolinamidine Nucleus: Synthesis and In Vitro Pharmacological Evaluation

FIORINO, FERDINANDO;SEVERINO, BEATRICE;MAGLI, ELISA;PERISSUTTI, ELISA;FRECENTESE, FRANCESCO;INCISIVO, GIUSEPPINA MARIA;CIANO, ANTONIO;SANTAGADA, VINCENZO;CALIENDO, GIUSEPPE
2012

Abstract

N’-Cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical for affinity to 5-HT1A receptors and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT2A and moderate to no affinity for other relevant receptors (5-HT1A, 5-HT2C, D1, D2, 1 and 2). N'-Cyano-N-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-picolinamidine (4l) with Ki = 0.000185 nM, was the most active and selective derivative for the 5-HT2A receptor compared to other serotoninergic, dopaminergic and adrenergic receptors.
2012
New Potent 5-HT2A Receptor Ligands Containing a N'-Cyanopicolinamidine Nucleus: Synthesis and In Vitro Pharmacological Evaluation / Fiorino, Ferdinando; Severino, Beatrice; Magli, Elisa; Perissutti, Elisa; Frecentese, Francesco; A., Esposito; Incisivo, GIUSEPPINA MARIA; Ciano, Antonio; P., Massarelli; C., Nencini; Santagada, Vincenzo; Caliendo, Giuseppe. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 47:(2012), pp. 520-529. [10.1016/j.ejmech.2011.11.023]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/415559
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