Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1

Abstract Synthesis of 2-adamantyl carbamate derivatives of piperidines and pyrrolidines led to the discovery of 9a with an IC 50 of 15.2 nM against human 11β-HSD1 in adipocytes. Optimization for increased adipocyte potency, metabolic stability and selectivity afforded 11k and 11l , both of which were >25% orally bioavailable in rat.