A novel 18β-glycyrrhetinic acid analogue as a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase 2

Using 18β-glycyrrhetinic acid as a template, the synthesis of a series of secondary amides at the 30-position is described and the effects of these modifications on the SAR of the 11β-hydroxysteroid dehydrogenase isozymes type 1 and 2 from the rat are investigated. An isoform selective inhibitor has been discovered and compound 5, N-(2-hydroxyethyl)-3β-hydroxy-11-oxo-18β-olean-12-en-30-oic acid amide, is highlighted as a very potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase 2 with an IC50 = 4 pM.