Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles.

Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles.

Bioorganic & medicinal chemistry letters (2010-05-11)

Scott P Webster, Margaret Binnie, Kirsty M M McConnell, Karen Sooy, Peter Ward, Michael F Greaney, Andy Vinter, T David Pallin, Hazel J Dyke, Matthew I A Gill, Ines Warner, Jonathan R Seckl, Brian R Walker

PMID20452767

RÉSUMÉ

Inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) show promise as drugs to treat metabolic disease and CNS disorders such as cognitive impairment. A series of 1,5-substituted 1H-tetrazole 11beta-HSD1 inhibitors has been discovered and chemically modified. Compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess good cellular potency in human and murine 11beta-HSD1 assays. A range of in vitro stabilities are observed in human liver microsome assays.