Identification of the Clinical Candidate (R)-(1-(4-Fluoropheny1)-6-((1methyl-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

被引：51

作者：

Hunt, Hazel J. ^{[1
]}

Belanoff, Joseph K. ^{[1
,2
]}

Walters, Iain ^{[2
]}

Gourdet, Benoit ^{[2
]}

Thomas, Jennifer ^{[2
]}

Barton, Naomi ^{[2
]}

Unitt, John ^{[2
]}

Phillips, Timothy ^{[2
]}

Swift, Denise ^{[2
]}

Eaton, Emily ^{[2
]}

机构：

[1] Corcept Therapeut, 149 Commonwealth Dr, Menlo Pk, CA 94025 USA

[2] BioCity, Sygnature Discovery, Pennyfoot St, Nottingham NG1 1GF, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 60卷 / 08期

关键词：

CUSHINGS-SYNDROME; DISEASE; MECHANISMS; HEALTH; GENE;

D O I：

10.1021/acs.jmedchem.7b00162

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 Sonic patients. Optimization pf the previously described fused azadecalin series of selective GR antagonists l'ed to the identification of CORT125134, which is currently being eValuateddp a phase 2 clinical study in patients with Cushing's syndrome.

引用

页码：3405 / 3421

页数：17

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