2. Academic Validation
  3. SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors

SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors

  • Bioorg Med Chem Lett. 2012 Dec 15;22(24):7653-8. doi: 10.1016/j.bmcl.2012.10.007.
Timothy Forsyth 1,  Patrick C Kearney,  Byung Gyu Kim,  Henry W B Johnson,  Naing Aay,  Arlyn Arcalas,  David S Brown,  Vicky Chan,  Jeff Chen,  Hongwang Du,  Sergey Epshteyn,  Adam A Galan,  Tai P Huynh,  Mohamed A Ibrahim,  Brian Kane,  Elena S Koltun,  Grace Mann,  Lisa E Meyr,  Matthew S Lee,  Gary L Lewis,  Robin T Noguchi,  Michael Pack,  Brian H Ridgway,  Xian Shi,  Craig S Takeuchi,  Peiwen Zu,  James W Leahy,  John M Nuss,  Ron Aoyama,  Stefan Engst,  Steven B Gendreau,  Robert Kassees,  Jia Li,  Shwu-Hwa Lin,  Jean-Francois Martini,  Thomas Stout,  Philip Tong,  John Woolfrey,  Wentao Zhang,  Peiwen Yu
Affiliations

Affiliation

  • 1 Exelixis, Department of Drug Discovery, 169 Harbor Way, South San Francisco, CA 94083, USA.
PMID: 23127890 DOI: 10.1016/j.bmcl.2012.10.007
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13775
    ≥98.0%, JAK2 Inhibitor