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.
Bingwei V Yang  1 ,  Wayne Vaccaro ,  Arthur M Doweyko ,  Lidia M Doweyko ,  Tram Huynh ,  David Tortolani ,  Steven G Nadler ,  Lorraine McKay ,  John Somerville ,  Deborah A Holloway ,  Sium Habte ,  David S Weinstein ,  Joel C Barrish
Affiliations
  • 1. Department of Discovery Chemistry, Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543, USA. [email protected]
PMID: 19321341 DOI: 10.1016/j.bmcl.2009.03.006
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.