RESUMEN

Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented.

Asunto(s)

Acenaftenos/farmacología , Acenaftenos/uso terapéutico , Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Acenaftenos/síntesis química , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Estructura Molecular , Ratas , Ratas Wistar , Relación Estructura-Actividad