The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 7; pp. 2340 - 2343
• Main Authors: Rimland, Joseph, Dunne, Angela, Hunjan, Suchete S., Sasse, Rosemary, Uings, Iain, Montanari, Dino, Caivano, Matilde, Shah, Poonam, Standing, David, Gray, David, Brown, David, Cairns, William, Trump, Ryan, Smith, Paul W., Bertheleme, Nicolas, D’Alessandro, Pier, Gul, Sheraz, Vimal, Mythily, Smith, David N., Watson, Stephen P.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-04-2010; Elsevier
• Subjects: Animals; Biological and medical sciences; Glucocorticoid receptor; Glucocorticoid receptor antagonist; GR antagonist; Hormones. Endocrine system; Medical sciences; Pharmacology. Drug treatments; Rats; Receptors, Glucocorticoid - antagonists & inhibitors; Receptors, Glucocorticoid - metabolism; Small Molecule Libraries - chemistry; Small Molecule Libraries - metabolism; Small Molecule Libraries - pharmacology; Structure-Activity Relationship; GR antagonist; Glucocorticoid receptor antagonist; Glucocorticoid receptor; Five membered ring; Isoxazole derivatives; Nitrogen heterocycle; Selectivity; In vitro; Chlorine Organic compounds; Bicyclic compound; Affinity; Carboxamide; Antagonist; Non steroid compound; Oxygen nitrogen heterocycle; Hormonal receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.01.133

The identification of novel, potent, non-steroidal/small molecule functional GR antagonist GSK1564023A PR is described. Associated structure–activity relationships and the process of optimisation of an initial HTS hit are also described.
The identification of novel, potent, non-steroidal/small molecule functional GR antagonist GSK1564023A selective over PR is described. Associated structure–activity relationships and the process of optimisation of an initial HTS hit are also described.