RESUMEN

A series of 5-phenyl-3-ureidobenzodiazepine-2,4-diones was synthesized and evaluated as cholecystokinin-B (CCK-B) receptor antagonists. Structure-activity relationship (SAR) studies revealed the importance of the N-1 substituent for potent and selective CCK-B affinity. Addition of substituents at the urea side chain provided in some cases more potent compounds. Moreover the introduction of bulky substituents such as adamantylmethyl at N-1 and resolution of the racemic ureas resulted in our lead compound GV150013.

Asunto(s)

Ansiolíticos/síntesis química , Benzodiazepinas/síntesis química , Receptores de Colecistoquinina/antagonistas & inhibidores , Animales , Ansiolíticos/química , Ansiolíticos/farmacología , Benzodiazepinas/química , Benzodiazepinas/farmacología , Callithrix , Corteza Cerebral/metabolismo , Cristalografía por Rayos X , Cobayas , Células HeLa , Humanos , Técnicas In Vitro , Membranas , Ratones , Modelos Moleculares , Páncreas/metabolismo , Ensayo de Unión Radioligante , Ratas , Receptor de Colecistoquinina A , Receptor de Colecistoquinina B , Receptores de Colecistoquinina/metabolismo , Estereoisomerismo , Relación Estructura-Actividad