Novel and selective spiroindoline-based inhibitors of Sky kinase

Bioorg Med Chem Lett. 2012 Jan 1;22(1):190-3. doi: 10.1016/j.bmcl.2011.11.036. Epub 2011 Nov 16.

Abstract

We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall.

MeSH terms

  • Absorption
  • Adenosine Triphosphate / chemistry
  • Administration, Oral
  • Animals
  • Binding Sites
  • Biological Availability
  • Chemistry, Pharmaceutical / methods*
  • Crystallography, X-Ray / methods
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Intestines / drug effects*
  • Models, Chemical
  • Platelet Aggregation
  • Rats
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / chemistry

Substances

  • Adenosine Triphosphate
  • Receptor Protein-Tyrosine Kinases
  • TYRO3 protein, human