RESUMEN

The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor ß (TRß) agonists is described. Compounds with >50× binding selectivity for TRß over TRα were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo.

Asunto(s)

Acetatos/farmacología , Diseño de Fármacos , Indoles/farmacología , Receptores beta de Hormona Tiroidea/agonistas , Acetatos/síntesis química , Acetatos/química , Relación Dosis-Respuesta a Droga , Humanos , Indoles/síntesis química , Indoles/química , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad