The synthesis and SAR of novel diarylsulfone 11β-HSD1 inhibitors

In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent efficacy in a non-human primate ex vivo pharmacodynamic model.

Graphical abstractThe synthesis and SAR of a series of diarylsulfone inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, selective, and orally bioavailable inhibitors demonstrating efficacy in a non-human primate ex vivo enzyme inhibition model.Figure optionsDownload full-size imageDownload as PowerPoint slide