Tetrahydroquinoline glucocorticoid receptor agonists: discovery of a 3-hydroxyl for improving receptor selectivity

Steven L Roach; Robert I Higuchi; Andrew R Hudson; Mark E Adams; Peter M Syka; Dale E Mais; Jeffrey N Miner; Keith B Marschke; Lin Zhi

doi:10.1016/j.bmcl.2010.11.047

Tetrahydroquinoline glucocorticoid receptor agonists: discovery of a 3-hydroxyl for improving receptor selectivity

Bioorg Med Chem Lett. 2011 Jan 1;21(1):168-71. doi: 10.1016/j.bmcl.2010.11.047. Epub 2010 Nov 11.

Authors

Steven L Roach¹, Robert I Higuchi, Andrew R Hudson, Mark E Adams, Peter M Syka, Dale E Mais, Jeffrey N Miner, Keith B Marschke, Lin Zhi

Affiliation

¹ Discovery Research, Ligand Pharmaceuticals, 11085 North Torrey Pines Road, Suite 300, La Jolla, CA 92037, USA. sroach@ligand.com

PMID: 21115247
DOI: 10.1016/j.bmcl.2010.11.047

Abstract

We have previously disclosed a series of glucocorticoid receptor (GR) ligands derived from 6-indole-1,2,3,4-tetrahydroquinolines through structure-activity relationship (SAR) of the pendent C6-indole ring. In parallel with this effort, we now report SAR of the tetrahydroquinoline A-ring that identified the importance of a C3 hydroxyl in improving GR selectivity within a series of non-steroidal GR agonists.

MeSH terms

Drug Evaluation, Preclinical
Protein Binding
Quinolines / chemical synthesis
Quinolines / chemistry*
Quinolines / pharmacology
Receptors, Glucocorticoid / agonists*
Receptors, Glucocorticoid / metabolism
Structure-Activity Relationship

Substances

Quinolines
Receptors, Glucocorticoid
1,2,3,4-tetrahydroquinoline