Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA.
Bioorg Med Chem Lett. 2013 Oct 1;23(19):5448-51. doi: 10.1016/j.bmcl.2013.06.085. Epub 2013 Jul 4.
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.
SAR 被用于进一步开发吲唑类非甾体糖皮质激素受体激动剂，该研究得到了本文所述的 GR LBD（配体结合域）-激动剂共晶结构的辅助。基于人源体外检测的发现分离型 GR 激动剂的研究进展，指导了对该化合物系列的优化，使其朝着具有良好选择性的部分激动剂方向发展，对其他核激素受体具有优异的选择性。
