Synthesis and biological evaluation of sulfonamidooxazoles and beta-keto sulfones: selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I

Bioorg Med Chem Lett. 2005 Jun 2;15(11):2865-9. doi: 10.1016/j.bmcl.2005.03.093.

Abstract

The design, synthesis, and biological evaluation of arylsulfonamidooxazoles as 11beta-HSD1 inhibitors and the serendipitous discovery of beta-keto sulfones as potent 11beta-HSD1 inhibitors are described here. These two classes of compounds are not active against 11beta-HSD2 and therefore may have significant therapeutic potential for metabolic syndrome, type 2 diabetes and related metabolic dysfunctions.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Oxazoles / chemical synthesis
  • Oxazoles / chemistry
  • Oxazoles / pharmacology*
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis
  • Sulfones / chemistry
  • Sulfones / pharmacology*

Substances

  • Enzyme Inhibitors
  • Oxazoles
  • Sulfones
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1