Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

Bioorg Med Chem. 2017 Jan 1;25(1):75-83. doi: 10.1016/j.bmc.2016.10.011. Epub 2016 Oct 11.

Abstract

Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC50 of 0.7nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.

Keywords: 4,5,6,7-Tetrahydro-furo[3,2-c]pyridine; 4-(2-Furanyl)pyrimidin-2-amine; JAK2 inhibitor; Kinase selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amines / pharmacology
  • Cell Line
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors*
  • Janus Kinase 2 / metabolism
  • Janus Kinase 3 / antagonists & inhibitors
  • Janus Kinase 3 / metabolism
  • Piperidines / pharmacology
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Pyrroles / pharmacology

Substances

  • Amines
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • JAK2 protein, human
  • Janus Kinase 2
  • Janus Kinase 3
  • pyrimidine