RESUMEN

A series of compounds possessing an N-substituted indoline-5-sulfonamide pharmacophore was prepared and evaluated for their human beta3 adrenergic receptor agonist activity. The SAR of a wide range of urea and heterocyclic substituents is discussed. 4-Octyl thiazole compound 8c was the most potent and selective compound in the series, with 2800-fold selectivity over beta1 binding and 1400-fold selectivity over beta2 binding.

Asunto(s)

Agonistas Adrenérgicos/síntesis química , Agonistas Adrenérgicos/farmacología , Indoles/síntesis química , Indoles/farmacología , Sulfonamidas/síntesis química , Sulfonamidas/farmacología , Animales , Células CHO , Cricetinae , Humanos , Modelos Químicos , Relación Estructura-Actividad