RESUMEN

A series of triamide derivatives bearing a benzothiazole core is shown to be potent microsomal triglyceride transfer protein (MTP) inhibitors. In order to minimize liver toxicity, these compounds have been optimized to have activity only in the enterocytes and have limited systemic bioavailability. Upon oral administration, selected analogs within this series have been further demonstrated to reduce food intake along with body weight and thereby improve glucose homeostasis and insulin sensitivity in a 28-day mice diet-induced obesity (DIO) model.

Asunto(s)

Benzotiazoles/química , Proteínas Portadoras/antagonistas & inhibidores , Descubrimiento de Drogas , Enterocitos/metabolismo , Animales , Benzotiazoles/farmacología , Benzotiazoles/uso terapéutico , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Enterocitos/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ratas , Ratas Sprague-Dawley