Fragment-based discovery of JAK-2 inhibitors

…, P Sprengeler, F Stappenbeck, R Steensma…

Index: Antonysamy, Stephen; Hirst, Gavin; Park, Frances; Sprengeler, Paul; Stappenbeck, Frank; Steensma, Ruo; Wilson, Mark; Wong, Melissa Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 1 p. 279 - 282

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Citation Number: 67

Abstract

Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.