Discovery of nonsteroidal glucocorticoid receptor ligands based on 6-indole-1,2,3,4-tetrahydroquinolines

A series of nonsteroidal glucocorticoid receptor (GR) ligands based on a 6-indole-1,2,3,4-tetrahydroquinoline scaffold are reported. Structure–activity relationship (SAR) of the pendent indole group identified compound 20 exhibiting good GR binding affinity (Ki = 1.5 nM) and 100- to 1000-fold selectivity over MR, PR, and AR while showing activity in an E-selectin repression assay.

Graphical abstractA series of nonsteroidal glucocorticoid receptor (GR) ligands based on a 6-indole-1,2,3,4-tetrahydroquinoline scaffold are reported. Structure–activity relationship (SAR) of the pendent indole group identified compound 20 exhibiting good GR binding affinity, receptor selectivity and E-selectin repression activity.Figure optionsDownload full-size imageDownload as PowerPoint slide