TRPV1 modulators: synthesis and in vitro evaluation of 1-heteroarylpiperidinecarboxamide and piperazinylurea derivatives

CONGIU, CENZO;ONNIS, VALENTINA;BALBONI, GIANFRANCO;Schiano Moriello, A;Di Marzo, V;De Petrocellis, L.

2015-01-01

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Abstract

A series of new 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives was synthesized and evaluated as TRPV1 modulators in a Ca2+ 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.