Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification ofN-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)methane-sulfonamides as Potent and SelectivehNaV1.7 Inhibitors for the Treatment of Pain

1.7 and human metabolic stability. Lead compounds 10, 13 (GNE-131), and 25 showed excellent potency, good in vitro metabolic stability, and low in vivo clearance in mouse, rat, and dog. Compound 13 also displayed excellent efficacy in a transgenic mouse model of induced pain.