RESUMEN
We herein describe the systematic approach used to develop new analogues of compound 2, recently identified as a potent and selective fatty acid amide hydrolase (FAAH) inhibitor. Aiming at identifying new scaffolds endowed with improved drug disposition properties with respect to the phenylpyrrole-based lead, we subjected it to two different structural modification strategies. This process allowed the identification of derivatives 4b and 5c as potent, reversible and non-competitive FAAH inhibitors.
Asunto(s)
Amidas/síntesis química , Amidohidrolasas/antagonistas & inhibidores , Pirroles/síntesis química , Amidas/química , Amidas/farmacología , Animales , Unión Competitiva , Humanos , Concentración 50 Inhibidora , Ratones , Modelos Moleculares , Pirroles/química , Pirroles/farmacología , Relación Estructura-ActividadRESUMEN
A new cationic polyhydroxylated lipid, characterized by a chiral template, was synthesized. It comes from an iridoid glucoside, as polyhydroxylated moiety. This lipid affords liposomes using cholesterol-like co-lipid. The liposomes had a spheroidal shape with a small size distribution.