Discovery of novel dihydro-9,10-ethano-anthracene carboxamides as glucocorticoid receptor modulators

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2139-43. doi: 10.1016/j.bmcl.2009.03.006. Epub 2009 Mar 9.

Abstract

A series of dihydro-9,10-ethano-anthracene-11-carboxamides as novel glucocorticoid receptor modulators is reported. SAR exploration identified compounds from this series displaying a promising dissociation profile in discriminating between transrepression and transactivation activities. 17a is a partial agonist of GR-mediated transactivation which elicits potent and efficacious transrepression in reporter gene assays. A hypothetical binding mode is provided which accounts for the induction of functional activity by a bridgehead methyl group.

Publication types

  • Comparative Study

MeSH terms

  • Anthracenes / chemistry
  • Anthracenes / pharmacology*
  • Cell Line
  • Crystallography, X-Ray
  • Drug Discovery* / methods
  • Glucocorticoids / chemistry
  • Glucocorticoids / pharmacology
  • Humans
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Receptors, Glucocorticoid / agonists
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Glucocorticoid / physiology
  • Structure-Activity Relationship

Substances

  • 9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid methyl ester
  • Anthracenes
  • Glucocorticoids
  • Receptors, Glucocorticoid