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

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

Bioorganic & medicinal chemistry letters (2008-06-03)

Steven L Roach, Robert I Higuchi, Mark E Adams, Yan Liu, Donald S Karanewsky, Keith B Marschke, Dale E Mais, Jeffrey N Miner, Lin Zhi

PMID18513967

摘要

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 (K(i)=1.5nM) and 100- to 1000-fold selectivity over MR, PR, and AR while showing activity in an E-selectin repression assay.