Discovery of adamantane ethers as inhibitors of 11β-HSD-1: Synthesis and biological evaluation

A novel class of adamantane ethers 11β-hydroxysteroid hydrogenase type I inhibitors has been discovered. These compounds have excellent HSD-1 potency and selectivity against HSD-2. The structure–activity relationships, selectivity, metabolism, PK, ex vivo pharmacodynamic data, and an X-ray crystal structure of one of these inhibitors bound to h-HSD-1 are discussed.

The synthesis and SAR of adamantane ethers are described as novel, potent and selective inhibitors of 11β-HSD-1. An X-ray crystal structure of one of these inhibitors bound to h-11β-HSD-1 is also described.Figure optionsDownload as PowerPoint slide