Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors

J Med Chem. 2005 Feb 10;48(3):710-22. doi: 10.1021/jm0408767.

Abstract

On the basis of ATP adenine, a series of adenine and purine derivatives was prepared and tested for their ability to inhibit a spectrum of disease-related kinases. There has been scant research investigating the potential of cosubstrate derived kinase inhibitors for other kinases than CDKs. Our inhibitor design combined the purine system from the original cosubstrate ATP and phenyl moieties in order to explore possible interactions with the different regions of the ATP binding site in several disease-related protein kinases. There have been a number of hits for the assayed substances, which led us to conclude that the spectrum of compounds may prove to be a valuable tool kit for the evaluation of bonding and selectivity patterns for a wide variety of kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • Binding, Competitive
  • Models, Molecular
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinases / chemistry*
  • Protein Kinases / metabolism
  • Purines / chemical synthesis*
  • Purines / chemistry
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / chemistry

Substances

  • Protein Kinase Inhibitors
  • Purines
  • Adenosine Triphosphate
  • Protein Kinases
  • p38 Mitogen-Activated Protein Kinases