5,6,7-trisubstituted 4-aminopyrido[2,3-d]pyrimidines as novel inhibitors of adenosine kinase

J Med Chem. 2003 Nov 20;46(24):5249-57. doi: 10.1021/jm030327l.

Abstract

The synthesis and structure-activity relationship of a series of 5,6,7-trisubstituted 4-aminopyrido[2,3-d]pyrimidines as novel nonnucleoside adenosine kinase inhibitors is described. A variety of alkyl, aryl, and heteroaryl substituents were found to be tolerated at the C5, C6, and C7 positions of the pyridopyrimidine core. These studies have led to the identification of analogues that are potent inhibitors of adenosine kinase with in vivo analgesic activity.

MeSH terms

  • Adenosine Kinase / antagonists & inhibitors*
  • Adenosine Kinase / chemistry
  • Analgesics / chemical synthesis*
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Animals
  • Cell Line, Tumor
  • Humans
  • Mice
  • Pain Measurement
  • Phosphorylation
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Pyridines
  • Pyrimidines
  • Adenosine Kinase