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

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 pre...

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Bibliographic Details
Published inJournal of medicinal chemistry Vol. 60; no. 8; pp. 3405 - 3421
Main Authors Hunt, Hazel J, Belanoff, Joseph K, Walters, Iain, Gourdet, Benoit, Thomas, Jennifer, Barton, Naomi, Unitt, John, Phillips, Timothy, Swift, Denise, Eaton, Emily
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 27.04.2017
Subjects
Animals
Chromatography, Liquid
Hep G2 Cells
Humans
Mass Spectrometry
Receptors, Glucocorticoid - antagonists & inhibitors
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ISSN0022-2623
1520-4804
DOI10.1021/acs.jmedchem.7b00162

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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.7b00162