RESUMEN

Following our research project aimed at obtaining new compounds with high affinity and selectivity toward alpha(1)-adrenoceptors (AR), a new class of piperazine derivatives was designed, synthesized and biologically tested. The new compounds 1-13 are characterized by a flavone system linked, through an ethoxy or propoxy spacer, to a phenyl- or pyridazinone-piperazine moiety. Biological data showed an interesting profile for the phenylpiperazine subclass found to have a nanomolar affinity toward alpha(1)-AR, and less pronounced affinity for alpha(2)-AR and the 5-HT(1A) serotoninergic receptor. A discussion on the structure-activity relationship (SAR) of such compounds is also reported, on the basis of the flavone substitution pattern, length and functionalization of the spacer, and disruption of the phenylpiperazine system.

Asunto(s)

Antagonistas Adrenérgicos alfa/síntesis química , Flavonoides/química , Piperazinas/síntesis química , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Receptores Adrenérgicos alfa 1/metabolismo , Antagonistas Adrenérgicos alfa/química , Antagonistas Adrenérgicos alfa/farmacología , Animales , Corteza Cerebral/metabolismo , Flavonas , Compuestos Heterocíclicos/síntesis química , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Piperazinas/química , Piperazinas/farmacología , Unión Proteica , Ensayo de Unión Radioligante , Ratas , Receptores de Serotonina 5-HT1/efectos de los fármacos , Receptores de Serotonina 5-HT1/metabolismo , Relación Estructura-Actividad