Identification of the Clinical Candidate (R)-(1-(4-Fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone (CORT125134): A Selective Glucocorticoid Receptor (GR) Antagonist

J Med Chem. 2017 Apr 27;60(8):3405-3421. doi: 10.1021/acs.jmedchem.7b00162. Epub 2017 Apr 17.


The nonselective glucocorticoid receptor (GR) antagonist mifepristone has been approved in the U.S. for the treatment of selected patients with Cushing's syndrome. While this drug is highly effective, lack of selectivity for GR leads to unwanted side effects in some patients. Optimization of the previously described fused azadecalin series of selective GR antagonists led to the identification of CORT125134, which is currently being evaluated in a phase 2 clinical study in patients with Cushing's syndrome.

MeSH terms

  • Animals
  • Chromatography, Liquid
  • Hep G2 Cells
  • Humans
  • Mass Spectrometry
  • Receptors, Glucocorticoid / antagonists & inhibitors*


  • Receptors, Glucocorticoid