Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists

  • Bioorg Med Chem Lett. 2013 Oct 1;23(19):5448-51. doi: 10.1016/j.bmcl.2013.06.085.
John L Gilmore  1 ,  James E Sheppeck 2nd ,  Jim Wang ,  T G Murali Dhar ,  Cullen Cavallaro ,  Arthur M Doweyko ,  Lorraine Mckay ,  Mark D Cunningham ,  Sium F Habte ,  Steven G Nadler ,  John H Dodd ,  John E Somerville ,  Joel C Barrish
Affiliations
  • 1. Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 23916594 DOI: 10.1016/j.bmcl.2013.06.085
Abstract

SAR was used to further develop an indazole class of non-steroidal Glucocorticoid Receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against Other nuclear hormone receptors.

Keywords
Dissociated; GR agonist; Glucocortocoids; Selective GR agonist.