Discovery Medicinal Chemistry, Discovery Research, GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA 19426-0989, USA.
Bioorg Med Chem Lett. 2010 Feb 15;20(4):1363-7. doi: 10.1016/j.bmcl.2010.01.003. Epub 2010 Jan 7.
A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent agonists of the human TGR5 G-protein-coupled receptor is described. Many analogues were readily accessible via solution-phase synthesis which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of potent exemplars (up to pEC50=9). Details of the SAR and optimization of this series are presented herein.
本文描述了从高通量筛选活动中鉴定出的一系列 3-芳基-4-异恶唑甲酰胺，它们是新型、强效的人类 TGR5 G 蛋白偶联受体激动剂。许多类似物可通过溶液相合成轻松获得，这导致了关键构效关系 (SAR) 的快速鉴定，并发现了有效的范例 (最高 pEC50=9)。本文介绍了该系列的 SAR 细节和优化。
