Discovery of quinolines as selective glucocorticoid receptor agonists

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5835-8. doi: 10.1016/j.bmcl.2010.07.125. Epub 2010 Aug 3.

Abstract

The dissociated glucocorticoid receptor (GR) agonist ZK 216348 is rendered GR-selective over other nuclear hormone receptors through replacing the methylbenzoxazine with a quinoline moiety. Compounds were shown to be efficacious in cell assays with respect to inflammation endpoints, along with reduced activity in a transactivation assay, hinting at an improved therapeutic window over corticosteroids.

MeSH terms

  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Drug Evaluation, Preclinical
  • Genes, Reporter / genetics
  • Humans
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology
  • Receptors, Glucocorticoid / agonists*
  • Receptors, Glucocorticoid / metabolism
  • Transcriptional Activation

Substances

  • Anti-Inflammatory Agents
  • Quinolines
  • Receptors, Glucocorticoid