Potent quinoxaline-based inhibitors of PDGF receptor tyrosine kinase activity. Part 2: the synthesis and biological activities of RPR127963 an orally bioavailable inhibitor

Bioorg Med Chem Lett. 2003 Sep 15;13(18):3097-100. doi: 10.1016/s0960-894x(03)00655-3.

Abstract

RPR127963 demonstrates an excellent pharmacokinetic profile in several species and was found to be efficacious in the prevention of restenosis in a Yucatan mini-pig model upon oral administration of 1-5 mg/kg. The in vitro selectivity profile and SAR of the highly optimized PDGF-R tyrosine kinase inhibitor are highlighted.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Cell Division / drug effects
  • Chemotaxis / drug effects
  • Collagen / biosynthesis
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / pharmacokinetics*
  • Quinoxalines / pharmacology
  • Rats
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Swine

Substances

  • Enzyme Inhibitors
  • Quinoxalines
  • Collagen
  • Cytochrome P-450 Enzyme System
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor