Author/Authors :
Daniel Kuzmich، نويسنده , , Tom Kirrane، نويسنده , , John Proudfoot، نويسنده , , Younes Bekkali، نويسنده , , Renee Zindell، نويسنده , , Laura Beck، نويسنده , , Richard Nelson، نويسنده , , Cheng-Kon Shih، نويسنده , , Alison J. Kukulka، نويسنده , , Zofia Paw، نويسنده , , Patty Reilly، نويسنده , , Rodney Deleon، نويسنده , , Mario Cardozo، نويسنده , , Gerald Nabozny، نويسنده , , David Thomson، نويسنده ,
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.
Keywords :
aromatase , IL-6 , Glucocorticoid receptor , anti-inflammatory , Glucocorticoid receptor agonist
