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C. Stanetty, L. Czollner, I. Koller, P. Shah, R. Gaware, T. Da Cunha, A. Odermatt, U. Jordis, P. Kosma, D. Classen-Houben:
"Synthesis of novel 3-amino and 29-hydroxamic acid derivatives of glycyrrhetinic acid as selective 11b-hydroxysteroid dehydrogenase 2 inhibitors";
Bioorganic & Medicinal Chemistry, 18 (2010), 7522 - 7541.

Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective
inhibitor of 11b-hydroxysteroid dehydrogenase (11b-HSD) type 1 and type 2. Whereas inhibition of
11b-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes,
11b-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain
forms of cancer. So far, no selective 11b-HSD2 inhibitor has been developed and neither animal
studies nor clinical trials have been reported based on 11b-HSD2 inhibition. Starting from the lead compound
glycyrrhetinic acid, novel triterpene type derivatives were synthesized and analyzed for their biological
activity against overexpressed human 11b-HSD1 and 11b-HSD2 in cell lysates. Several
hydroxamic acid derivatives showed high selectivity for 11b-HSD2. The most potent and selective compound
is active against human 11b-HSD2 in the low nanomolar range with a 350-fold selectivity over
human 11b-HSD1.

http://dx.doi.org/10.1016/j.bmc.2010.08.046