RESUMEN

A series of new 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives was synthesized and evaluated as TRPV1 modulators in a Ca(2+) channel assay in HEK-293 cells overexpressing the human recombinant TRPV1 channel. Structural variations in the putative key portions of the molecules afforded several compounds endowed with agonist and/or antagonist/desensitizing activity at low micromolar concentration. As promising examples from this series, the piperidine-3-carboxamide derivative 31 exerts agonist/desensitizing activity at low micromolar concentration, while piperazinylurea derivatives 39 and 41 act as antagonists with sub-micromolar potency.

Asunto(s)

Amidas/farmacología , Piperidinas/farmacología , Canales Catiónicos TRPV/agonistas , Canales Catiónicos TRPV/antagonistas & inhibidores , Urea/farmacología , Amidas/síntesis química , Amidas/química , Relación Dosis-Respuesta a Droga , Células HEK293 , Humanos , Estructura Molecular , Piperidinas/síntesis química , Piperidinas/química , Relación Estructura-Actividad , Urea/análogos & derivados , Urea/química