The discovery of reverse tricyclic pyridone JAK2 inhibitors. Part 2: Lead optimization

…, M Katcher, A Northrup, C White, C Rosenstein…

文献索引：Siu, Tony; Kumarasinghe, Sathyajith E.; Altman, Michael D.; Katcher, Matthew; Northrup, Alan; White, Catherine; Rosenstein, Craig; Mathur, Anjili; Xu, Lin; Chan, Grace; Bachman, Eric; Bouthillette, Melaney; Dinsmore, Christopher J.; Marshall, C. Gary; Young, Jonathan R. Bioorganic and Medicinal Chemistry Letters, 2014 , vol. 24, # 6 p. 1466 - 1471

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被引用次数: 2

摘要

Abstract This communication discusses the discovery of novel reverse tricyclic pyridones as inhibitors of Janus kinase 2 (JAK2). By using a kinase cross screening approach coupled with molecular modeling, a unique inhibitor–water interaction was discovered to impart excellent broad kinase selectivity. Improvements in intrinsic potency were achieved by utilizing a rapid library approach, while targeted structural changes to lower lipophilicity ...