Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors

Bioorg Med Chem Lett. 2012 Oct 1;22(19):6212-7. doi: 10.1016/j.bmcl.2012.08.020. Epub 2012 Aug 10.

Abstract

Two classes of ACK1 inhibitors, 4,5,6-trisubstituted furo[2,3-d]pyrimidin4-amines and 4,5,6-trisubstituted 7H-pyrrolo[2,3-d]pyrimidin-4-amines, were discovered and evaluated as ACK1 inhibitors. Further structural refinement led to the identification of potent and selective dithiolane inhibitor 37.

MeSH terms

  • Dose-Response Relationship, Drug
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 7H-pyrrolo(2,3-d)pyrimidin-4-amine
  • Furans
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • furo(2,3-d)-pyrimidin-4-amine
  • Protein-Tyrosine Kinases
  • TNK2 protein, human