Medicinal chemistry of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)

J Med Chem. 2014 Jun 12;57(11):4466-86. doi: 10.1021/jm4014746. Epub 2013 Dec 13.


11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is the enzyme primarily responsible for the regulation of intracellular cortisol levels. Inhibition of 11β-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. Emerging literature also supports a potential role in the treatment of other unmet medical needs including Alzheimer's disease, vascular inflammation, cardiovascular disease, and glaucoma. The aim of this article is to review the medicinal chemistry literature around small molecule approaches to developing synthetic inhibitors of 11β-HSD1 and to highlight key compounds that have resulted from the efforts of both industrial and academic groups. The reported data from 11β-HSD1 inhibitors that have progressed into the clinic are summarized followed by a perspective from the authors.

Publication types

  • Review

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology
  • Clinical Trials as Topic
  • Glaucoma / drug therapy
  • Glaucoma / enzymology
  • Glucocorticoids / metabolism
  • Humans
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / enzymology


  • Glucocorticoids
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1