Identification of dissociated non-steroidal glucocorticoid receptor agonists |
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| Authors: | Kuzmich Daniel Kirrane Tom Proudfoot John Bekkali Younes Zindell Renee Beck Laura Nelson Richard Shih Cheng-Kon Kukulka Alison J Paw Zofia Reilly Patty Deleon Rodney Cardozo Mario Nabozny Gerald Thomson David |
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| Institution: | Medicinal Chemistry Department, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA. dkuzmich@rdg.boehringer-ingelheim.com |
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| 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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