RESUMEN
A series of bezafibrate ester prodrugs 1-7 were synthesized and evaluated for hypolipidemic activity in Swiss Albino mice (SAM). Bezafibrate (1a), a hypolipidemic drug was used as a reference compound for data comparison. Among the synthesized compounds, prodrug 7 showed superior activities in decreasing triglyceride up to 30% in mice plasma after oral administration of 50mg/kg/day for 8 days. Prodrugs 2, 3, 5, 6, and 7 were found to be more lipophilic than bezafibrate (1a), indicated by partition coefficients measured in octanol-buffer system at pH 7.4. On the basis of in vivo studies, prodrug 7 emerged as new potent hypolipidemic agent.
Asunto(s)
Bezafibrato/análogos & derivados , Bezafibrato/síntesis química , Hipolipemiantes/síntesis química , Profármacos/síntesis química , Administración Oral , Animales , Bezafibrato/farmacología , Esquema de Medicación , Estabilidad de Medicamentos , Ésteres , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Hipolipemiantes/farmacología , Masculino , Ratones , Octanoles , Profármacos/farmacología , Relación Estructura-Actividad , Triglicéridos/sangre , AguaRESUMEN
A series of novel fenofibric acid ester prodrugs 1c-1h were synthesized and evaluated with the aim of obtaining potent hypolipidemic agents. Prodrugs 1c and 1d exhibited potent hypochlolesterolemic activity, lowering the mice plasma triglyceride level up to 47% in Swiss albino mice after oral administration of 50 mg/kg/day for 8 days. Fenofibric acid ester prodrugs 1c-1h were found lipophilic like fenofibrate (1b), indicated by partition coefficients measured in octanol-buffer system at pH 7.4. On the basis of in vivo studies, prodrugs 1c and 1d emerged as potent hypolipidemic agents.