Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2

Bioorg Med Chem Lett. 2005 Feb 15;15(4):863-7. doi: 10.1016/j.bmcl.2004.12.073.

Abstract

The protein structure guided design of a series of pyrazolo[1,5-a]pyrimidines with high potency for human cyclin-dependent kinase 2 (CDK2) is described. Some examples were shown to inhibit the growth of human colon tumour cells, were equipotent for CDK1 and were selective against GSK-3beta and other kinases.

MeSH terms

  • CDC2 Protein Kinase / antagonists & inhibitors
  • CDC2-CDC28 Kinases / antagonists & inhibitors*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase 2
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Pyrimidines
  • CDC2 Protein Kinase
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2