Optimization of highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase

Bioorg Med Chem Lett. 2013 Feb 15;23(4):1051-5. doi: 10.1016/j.bmcl.2012.12.028. Epub 2012 Dec 20.

Abstract

Optimization of the ADME properties of a series of 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase resulted in the identification of highly selective compounds with properties suitable for use as in vitro and in vivo tools to probe the effects of Sky inhibition.

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology
  • Animals
  • Humans
  • Mice
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Amides
  • Protein Kinase Inhibitors
  • Pyrimidines
  • 2,4-diaminopyrimidine
  • Receptor Protein-Tyrosine Kinases
  • TYRO3 protein, human