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.
Steven L Roach  1 ,  Robert I Higuchi ,  Andrew R Hudson ,  Mark E Adams ,  Peter M Syka ,  Dale E Mais ,  Jeffrey N Miner ,  Keith B Marschke ,  Lin Zhi
Affiliations
  • 1. Discovery Research, Ligand Pharmaceuticals, 11085 North Torrey Pines Road, Suite 300, La Jolla, CA 92037, USA. [email protected]
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.