RESUMEN

Dopamine (D(2)) partial agonists (D2PAs) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics. Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D(2) partial agonists. These compounds have good selectivity, CNS drug-like properties and tunable D(2) partial agonism. One of the key compounds, 8h, has good in vitro/in vivo ADME characteristics, and is active in a rat amphetamine-induced locomotor activity model.

Asunto(s)

Benzazepinas/síntesis química , Benzazepinas/farmacología , Agonistas de Dopamina/síntesis química , Agonistas de Dopamina/farmacología , Receptores de Dopamina D2/agonistas , Animales , Antipsicóticos/síntesis química , Antipsicóticos/química , Antipsicóticos/farmacología , Benzazepinas/química , Bioensayo , Modelos Animales de Enfermedad , Agonistas de Dopamina/química , Agonismo Parcial de Drogas , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Unión Proteica/efectos de los fármacos , Ratas , Relación Estructura-Actividad