The synthesis and SAR of novel diarylsulfone 11β-HSD1 inhibitors

Bioorg Med Chem Lett. 2010 Dec 1;20(23):7071-5. doi: 10.1016/j.bmcl.2010.09.097. Epub 2010 Sep 29.

Abstract

In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent efficacy in a non-human primate ex vivo pharmacodynamic model.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors
  • Animals
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacokinetics
  • Humans
  • Pharmacokinetics
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis*
  • Sulfones / chemistry
  • Sulfones / pharmacokinetics

Substances

  • Enzyme Inhibitors
  • Sulfones
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • HSD11B1 protein, human