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.
Andrew R Hudson  1 ,  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
Affiliations
  • 1. Discovery Research, Ligand Pharmaceuticals, La Jolla, CA 92037, USA. [email protected]
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.