Recent advances in the discovery of 11beta-HSD1 inhibitors

Glucocorticoids are steroid hormones that regulate several physiological processes, and modulation of glucocorticoid action has been implicated as a potential treatment for a variety of diseases, including metabolic syndrome, inflammation and age-related cognitive decline. 11b-Hydroxysteroid dehydrogenase type 1 (11b-HSD1) is an enzyme that is involved in glucocorticoid regulation by catalyzing the conversion of inactive cortisone to its active form cortisol. Rodent models have demonstrated that the inhibition of 11b-HSD1 can improve components of metabolic syndrome, such as insulin resistance and dyslipidemia, and several laboratories are exploring small-molecule 11b-HSD1 inhibitors as a treatment for metabolic syndrome, as well as for type 2 diabetes. This review discusses progress in the development of key chemical classes of 11b-HSD1 inhibitors, with a focus on advanced compounds and recently disclosed structures.