New potent 5-HT2A receptor ligands containing an N %26apos;-cyanopicolinamidine nucleus: Synthesis and in vitro pharmacological evaluation

作者：Fiorino Ferdinando; Severino Beatrice; Magli Elisa; Perissutti Elisa; Frecentese Francesco; Esposito Antonella; Incisivo Giuseppina Maria; Ciano Antonio; Massarelli Paola; Nencini Cristina; Santagada Vincenzo; Caliendo Giuseppe^*

来源：European Journal of Medicinal Chemistry, 2012, 47: 520-529.

DOI：10.1016/j.ejmech.2011.11.023

• N %26apos
• -cyanopicolinamidine derivatives
• 5-HT1A ligands
• 5-HT2A ligands
• Binding assays

N%26apos;-cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to serotonin 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, alpha(1) and alpha(2)). N%26apos;-cyano-N-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-Picolina-midine (41) with K-i = 0.000185 nm, was the most active and selective derivative for the 5-HT2A receptor compared to other serotoninergic, dopaminergic and adrenergic receptors.

• 出版日期2012-1