4BBE

Sar and in Vivo Evaluation of 4-Aryl-2-Aminoalkylpyrimidines as Potent and Selective Janus Kinase 2 (Jak2) Inhibitors

Forsyth, T., Kearney, P.C., Kim, B.G., Johnson, H.W.B., Aay, N., Arcalas, A., Brown, D.S., Chan, V., Chen, J., Du, H., Epshteyn, S., Galan, A.A., Huynh, T.P., Ibrahim, M.A., Kane, B., Koltun, E., Mann, G., Meyr, L.E., Lee, M.S., Lewis, G.L., Noguchi, R.T., Pack, M., Ridgway, B.H., Shi, X., Takeuchi, C.S., Zu, P., Leahy, J.W., Nuss, J.M., Aoyama, R., Engst, S., Gendreau, S.B., Kassees, R., Li, J., Lin, S.-H., Martini, J.-F., Stout, T., Tong, P., Woolfrey, J., Zhang, W., Yu, P.

(2012) Bioorg Med Chem Lett 22: 7653

• PubMed: 23127890 Search on PubMed
• DOI: https://doi.org/10.1016/j.bmcl.2012.10.007
• Primary Citation of Related Structures:  
  4BBE, 4BBF


• PubMed Abstract: 
  

  We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives as potent and selective JAK2 inhibitors. High throughput screening of our in-house compound library led to the identification of hit 1, from which optimization resulted in the discovery of highly potent and selective JAK2 inhibitors. Advanced lead 10d demonstrated a significant dose-dependent pharmacodynamic and antitumor effect in a mouse xenograft model. Based upon the desirable profile of 10d (XL019) it was advanced into clinical trials.

   View More

---

Organizational Affiliation: 

Exelixis, Department of Drug Discovery, 169 Harbor Way, South San Francisco, CA 94083, USA.