Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA.
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6645-9. doi: 10.1016/j.bmcl.2013.10.047. Epub 2013 Oct 31.
A class of arylsulfonamide glucocorticoid receptor agonists that contains a substituted phenyl group as a steroid A-ring mimetic is reported. The structural design and SAR that provide the functional switching of a GR antagonist to an agonist is described. A combination of specific hydrogen bonding and lipophilic elements on the A-ring moiety is required to achieve potent GR agonist activity. This study culminated in the identification of compound 23 as a potent GR agonist with selectivity over the PR and MR nuclear hormone receptors.
报告了一类芳基磺胺类糖皮质激素受体激动剂，其中包含一个取代的苯环作为甾体 A 环类似物。描述了提供从 GR 拮抗剂到激动剂的功能转换的结构设计和 SAR。在 A 环部分上需要特定的氢键和疏水性元素的组合才能实现有效的 GR 激动剂活性。这项研究的最终结果是确定了化合物 23 作为一种有效的 GR 激动剂，对 PR 和 MR 核激素受体具有选择性。
