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.
Hazel J Hunt  1 ,  Joseph K Belanoff  1 ,  Iain Walters  2 ,  Benoit Gourdet  2 ,  Jennifer Thomas  2 ,  Naomi Barton  2 ,  John Unitt  2 ,  Timothy Phillips  2 ,  Denise Swift  2 ,  Emily Eaton  2
Affiliations
  • 1. Corcept Therapeutics , 149 Commonwealth Drive, Menlo Park, California 94025, United States.
  • 2. Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
PMID: 28368581 DOI: 10.1021/acs.jmedchem.7b00162
Abstract

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.

Products