Synthesis and evaluation of piperidine urea derivatives as efficacious 11β-hydroxysteroid dehydrogenase type 1 inhibitors in diabetic ob/ob mice

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has attracted considerable attention as a potential target for the treatment of diabetes and metabolic syndrome. Herein we report the design, synthesis and efficacy evaluation of novel amide and urea 11β-HSD1 inhibitors. Structure–activity relationship studies led to the identification of 10c, which was efficacious in a diabetic ob/ob mouse model and reduced fasting and non-fasting blood glucose levels after ip dosing.

Graphical abstractNovel piperidine ureas were designed as potent 11β-HSD1 inhibitors. SAR studies led to the identification of 10c, which reduced fasting and non-fasting blood glucose levels after ip dosing in diabetic ob/ob mice.Figure optionsDownload full-size imageDownload as PowerPoint slide