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

Abstract

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.

• Authors: 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
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 11 Pg. 3265-71 (Jun 01 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20452767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Tetrazoles
• 11-beta-Hydroxysteroid Dehydrogenase Type 1

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 1 (antagonists & inhibitors)
• Animals
• Enzyme Inhibitors (pharmacology)
• Humans
• Mice
• Models, Molecular
• Tetrazoles (pharmacology)