2. Academic Validation
  3. Identification of dissociated non-steroidal glucocorticoid receptor agonists

Identification of dissociated non-steroidal glucocorticoid receptor agonists

  • Bioorg Med Chem Lett. 2007 Sep 15;17(18):5025-31. doi: 10.1016/j.bmcl.2007.07.031.
Daniel Kuzmich 1,  Tom Kirrane,  John Proudfoot,  Younes Bekkali,  Renee Zindell,  Laura Beck,  Richard Nelson,  Cheng-Kon Shih,  Alison J Kukulka,  Zofia Paw,  Patty Reilly,  Rodney Deleon,  Mario Cardozo,  Gerald Nabozny,  David Thomson
Affiliations

Affiliation

  • 1 Medicinal Chemistry Department, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA. dkuzmich@rdg.boehringer-ingelheim.com
PMID: 17692519 DOI: 10.1016/j.bmcl.2007.07.031
Abstract

A new series of ligands for the Glucocorticoid Receptor (GR) is described. SAR development was guided by docking 3 into the GR active site and optimizing an unsubstituted phenyl ring for key interactions found in the steroid A-ring binding pocket. To identify compounds with an improved side effect profile over marketed Steroids the functional activity of compounds was evaluated in cell based assays for transactivation (aromatase) and transrepression (IL-6). Through this effort, 36 has been identified as a partial agonist with a dissociated profile in these cell based assays.

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