Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck II

Bioorg Med Chem Lett. 2000 Oct 2;10(19):2171-4. doi: 10.1016/s0960-894x(00)00442-x.

Abstract

Pyrrolo[2,3-d]pyrimidines containing a 5-(4-phenoxyphenyl) substituent are novel, potent and selective inhibitors of lck in vitro. Exploration of C-6 position of the pyrrolo[2,3-d]pyrimidine and the terminal phenyl group structure-activity relationship (SAR) is detailed. Compound 1 is orally active in animal models.

MeSH terms

  • Animals
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / chemistry
  • Mice
  • Molecular Structure
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, TIE-2
  • Receptors, Growth Factor / antagonists & inhibitors
  • Receptors, Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor

Substances

  • Enzyme Inhibitors
  • Pyrimidines
  • Pyrroles
  • Receptors, Growth Factor
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-2
  • Receptors, Vascular Endothelial Growth Factor
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Proto-Oncogene Proteins pp60(c-src)