Discovery of orally available tetrahydroquinoline-based glucocorticoid receptor agonists

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

doi:10.1016/j.bmcl.2011.01.093

Discovery of orally available tetrahydroquinoline-based glucocorticoid receptor agonists

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1697-700. doi: 10.1016/j.bmcl.2011.01.093. Epub 2011 Jan 26.

Authors

Andrew R Hudson¹, Robert I Higuchi, Steven L Roach, Mark E Adams, Angela Vassar, Peter M Syka, Dale E Mais, Jeffrey N Miner, Keith B Marschke, Lin Zhi

Affiliation

¹ Discovery Research, Ligand Pharmaceuticals, La Jolla, CA 92037, USA. andyrhudson@gmail.com

PMID: 21316964
DOI: 10.1016/j.bmcl.2011.01.093

Abstract

A series of tetrahydroquinoline derivatives were synthesized and profiled for their ability to act as glucocorticoid receptor selective modulators. Structure-activity relationships of the tetrahydroquinoline B-ring lead to the discovery of orally available GR-selective agonists with high in vivo activity.

MeSH terms

Administration, Oral
Animals
Drug Discovery
Enzyme-Linked Immunosorbent Assay
Humans
Quinolines / administration & dosage
Quinolines / chemistry
Quinolines / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid / agonists*
Structure-Activity Relationship

Substances

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