Synthesis and Biological Evaluation of Cyclic Sulfamide Derivatives as 11β-Hydroxysteroid Dehydrogenase 1 Inhibitors

Abstract

A new series of cyclic sulfamide derivatives were synthesized and evaluated for their ability to inhibit 11β-HSD1. Among this series, 18e showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, and pharmacokinetic and safety profiles (hERG, CYP, and acute toxicity). Additionally, 18e exhibited good in vivo efficacy in rat and monkey models.