Discovery and optimisation of a selective non-steroidal glucocorticoid receptor antagonist

Bioorg Med Chem Lett. 2011 Jan 1;21(1):137-40. doi: 10.1016/j.bmcl.2010.11.054. Epub 2010 Nov 16.

Abstract

High-throughput screening of 3.87 million compounds delivered a novel series of non-steroidal GR antagonists. Subsequent rounds of optimisation allowed progression from a non-selective ligand with a poor ADMET profile to an orally bioavailable, selective, stable, glucocorticoid receptor antagonist.

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • High-Throughput Screening Assays
  • Humans
  • Hydrocortisone / chemistry
  • Microsomes / metabolism
  • Rats
  • Receptors, Glucocorticoid / antagonists & inhibitors*
  • Receptors, Glucocorticoid / metabolism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacokinetics

Substances

  • Receptors, Glucocorticoid
  • Sulfonamides
  • Hydrocortisone