Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369901 | Bioorganic & Medicinal Chemistry Letters | 2014 | 7 Pages |
Abstract
The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign gave compound 41, a nanomolar inhibitor of hXO with efficacy in the hyperuricemic rat model after oral dosing.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Johan Evenäs, Fredrik Edfeldt, Matti Lepistö, Naila Svitacheva, Anna Synnergren, Britta Lundquist, Mia Gränse, Anna Rönnholm, Mikael Varga, John Wright, Min Wei, Sherrie Yue, Junfeng Wang, Chong Li, Xuan Li, Gang Chen, Yong Liao, Gang Lv, Ann Tjörnebo,