Rational design of 4,5-disubstituted-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-ones as a novel class of inhibitors of epidermal growth factor receptor (EGF-R) and Her2(p185(erbB)) tyrosine kinases

Bioorg Med Chem Lett. 2002 Aug 19;12(16):2153-7. doi: 10.1016/s0960-894x(02)00364-5.

Abstract

A novel class of 4,5-disubstituted-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-ones has been discovered as potent and selective inhibitors of the EGF-R tyrosine kinase family. These compounds selectively inhibit EGF-R kinase activity at low nanomolar concentration and tyrosine autophosphorylation in cells expressing EGF-R or Her2 (p185(erbB)). Structure-activity relationships (SARs) for this class of compounds are presented.

MeSH terms

  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • ErbB Receptors / antagonists & inhibitors*
  • Molecular Structure
  • Phosphorylation / drug effects
  • Phosphotyrosine / metabolism
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry
  • Pyrimidinones / pharmacology*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Pyrimidinones
  • Phosphotyrosine
  • ErbB Receptors
  • Receptor, ErbB-2