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

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

doi:10.1016/j.bmcl.2008.05.029

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

Bioorg Med Chem Lett. 2008 Jun 15;18(12):3504-8. doi: 10.1016/j.bmcl.2008.05.029. Epub 2008 May 11.

Authors

Steven L Roach¹, Robert I Higuchi, Mark E Adams, Yan Liu, Donald S Karanewsky, Keith B Marschke, Dale E Mais, Jeffrey N Miner, Lin Zhi

Affiliation

¹ Discovery Research, Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, CA 92121, USA. sroach@ligand.com

PMID: 18513967
DOI: 10.1016/j.bmcl.2008.05.029

Abstract

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.

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Binding Sites
Drug Evaluation, Preclinical
Indoles / chemical synthesis
Indoles / chemistry
Indoles / pharmacology*
Ligands
Molecular Structure
Quinolines / chemical synthesis
Quinolines / chemistry
Quinolines / pharmacology*
Receptors, Glucocorticoid / drug effects*
Stereoisomerism
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents, Non-Steroidal
Indoles
Ligands
Quinolines
Receptors, Glucocorticoid