4-(Phenylsulfonamidomethyl)benzamides as Potent and Selective Inhibitors of the 11β-Hydroxysteroid Dehydrogenase Type 1 with Efficacy in Diabetic ob/ob Mice.

Abstract Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have considerable potential as treatments for type 2 diabetes. Presented herein are the syntheses, structure–activity relationships, and efficacy evaluation of 4-(phenylsulfonamidomethyl)benzamides as 11β-HSD1 inhibitors. Through modification of our initial lead 5, we have identified potent and selective 11β-HSD1 inhibitors, such as 11n, which demonstrated improved glycemic control, decreased serum lipids, and enhanced insulin sensitivity when dosed ip in diabetic ob/ob mice.