RESUMEN

Herein we present the expedient synthesis of endomorphin-1 analogues containing stereoisomeric ß2-homo-Freidinger lactam-like scaffolds ([Amo2]EM), and we discuss opioid receptor (OR) affinity, enzymatic stability, functional activity, in vivo antinociceptive effects, and conformational and molecular docking analysis. Hence, H-Tyr-Amo-Trp-PheNH2 resulted to be a new chemotype of highly stable, selective, partial KOR agonist inducing analgesia, therefore displaying great potential interest as a painkiller possibly with reduced harmful side effects.

Asunto(s)

Analgésicos/química , Analgésicos/farmacología , Dipéptidos/química , Compuestos Heterocíclicos/química , Oligopéptidos/química , Oligopéptidos/farmacología , Receptores Opioides kappa/agonistas , Analgésicos/síntesis química , Analgésicos/metabolismo , Animales , Ratones , Simulación del Acoplamiento Molecular , Oligopéptidos/síntesis química , Oligopéptidos/metabolismo , Conformación Proteica , Receptores Opioides kappa/química , Receptores Opioides kappa/metabolismo