Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists
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- 作者：John L. Gilmore ; James E. Sheppeck II ; 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
- 关键词：Glucocortocoids ; GR agonist ; Dissociated ; Selective GR agonist
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：1 October, 2013
- 年：2013
- 卷：23
- 期：19
- 页码：5448-5451
- 全文大小：658 K
文摘
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.