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.
Boyle
Craig D
CD
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. craig.boyle@spcorp.com
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000201:enzymology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1