Highly tractable, sub-nanomolar non-steroidal glucocorticoid receptor agonists

Starting from a non-steroidal glucocorticoid agonist aryl pyrazole derivative, the NFκB agonist activity was optimised in an iterative process from pIC50 7.5 (for 7), to pIC50 10.1 (for 38E1). An explanation for the SAR observed based is presented along with a proposed docking of 38E1 into the active site of the glucocorticoid receptor.

The discovery of 38E1 as a highly potent non-steroidal glucocorticoid agonist is described.Figure optionsDownload as PowerPoint slide