Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors

  • Bioorg Med Chem Lett. 2010 Apr 15;20(8):2609-13. doi: 10.1016/j.bmcl.2010.02.056.
Carole Pissot-Soldermann  1 ,  Marc Gerspacher ,  Pascal Furet ,  Christoph Gaul ,  Philipp Holzer ,  Clive McCarthy ,  Thomas Radimerski ,  Catherine H Regnier ,  Fabienne Baffert ,  Peter Drueckes ,  Gisele A Tavares ,  Eric Vangrevelinghe ,  Francesca Blasco ,  Giorgio Ottaviani ,  Flavio Ossola ,  Julien Scesa ,  Janitha Reetz
Affiliations
  • 1. Novartis Institutes for Biomedical Research, Novartis Pharma AG, WKL-136.4.96, CH-4002 Basel, Switzerland. [email protected]
PMID: 20231096 DOI: 10.1016/j.bmcl.2010.02.056
Abstract

We have designed and synthesized a novel series of 2,8-diaryl-quinoxalines as Janus kinase 2 inhibitors. Many of the inhibitors show low nanomolar activity against JAK2 and potently suppress proliferation of SET-2 cells in vitro. In addition, compounds from this series have favorable rat pharmacokinetic properties suitable for in vivo efficacy evaluation.