Discovery of quinolines as selective glucocorticoid receptor agonists

The dissociated glucocorticoid receptor (GR) agonist ZK 216348 is rendered GR-selective over other nuclear hormone receptors through replacing the methylbenzoxazine with a quinoline moiety. Compounds were shown to be efficacious in cell assays with respect to inflammation endpoints, along with reduced activity in a transactivation assay, hinting at an improved therapeutic window over corticosteroids.

Graphical abstractThe dissociated glucocorticoid receptor (GR) agonist ZK 216348 (1) is rendered GR-selective by replacing the methylbenzoxazine moiety with quinolines. Compounds were shown to be efficacious in vitro in reporter gene and cell assays, along with reduced activity in a transactivation assay, hinting at an improved therapeutic window over corticosteroids.Figure optionsDownload full-size imageDownload as PowerPoint slide