5-Functionalized indazoles as glucocorticoid receptor agonists

An indazole based series of glucocorticoid receptor agonists is reported. The SAR exploration of this scaffold yielded compounds with nanomolar affinity for the glucocorticoid receptor with indications of selectivity for the preferred transrepression mechanism; in vivo efficacy was observed in the mouse LPS induced TNFα model for compound 28.

Graphical abstractAn indazole based series of glucocorticoid receptor (GR) agonists is reported and the SAR disclosed. The series yielded potent compounds for the GR with indications of selectivity for the preferred transrepression mechanism.Figure optionsDownload full-size imageDownload as PowerPoint slide