Discovery and optimization of novel, non-steroidal glucocorticoid receptor modulators

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4901-5. doi: 10.1016/j.bmcl.2007.06.036. Epub 2007 Jun 13.

Abstract

A virtual screening approach comprising a 3-D similarity search based on known GR modulators was used to identify a novel series of non-steroidal glucocorticoid receptor (GR) antagonists. Optimization of the initial hit to provide potent compounds which exhibit good selectivity against other steroidal nuclear hormone receptors is described.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antidepressive Agents / chemical synthesis*
  • Antidepressive Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Evaluation, Preclinical
  • Glucocorticoids / chemistry*
  • Humans
  • Kinetics
  • Models, Chemical
  • Molecular Conformation
  • Rats
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Steroid / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antidepressive Agents
  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Receptors, Steroid