Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors

…, J Blaney, C Chang, C Eigenbrot, S Flynn…

Index: Hanan, Emily J.; Van Abbema, Anne; Barrett, Kathy; Blair, Wade S.; Blaney, Jeff; Chang, Christine; Eigenbrot, Charles; Flynn, Sean; Gibbons, Paul; Hurley, Christopher A.; Kenny, Jane R.; Kulagowski, Janusz; Lee, Leslie; Magnuson, Steven R.; Morris, Claire; Murray, Jeremy; Pastor, Richard M.; Rawson, Tom; Siu, Michael; Ultsch, Mark; Zhou, Aihe; Sampath, Deepak; Lyssikatos, Joseph P. Journal of Medicinal Chemistry, 2012 , vol. 55, # 22 p. 10090 - 10107

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Citation Number: 25

Abstract

The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in discovering selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo [1, 5-a] pyrimidine scaffold as a potent inhibitor of Jak2. Optimization of lead compounds 7a–b and 8 in this chemical series for activity against Jak2, selectivity against other Jak family kinases, ...