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

Bioorg Med Chem Lett. 2010 Jun 1;20(11):3265-71. doi: 10.1016/j.bmcl.2010.04.055. Epub 2010 Apr 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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