Anilinopyrazole as selective CDK2 inhibitors: design, synthesis, biological evaluation, and X-ray crystallographic analysis

Bioorg Med Chem Lett. 2003 Sep 15;13(18):2985-8. doi: 10.1016/s0960-894x(03)00630-9.

Abstract

A novel series of anilinopyrazoles has been designed based on the X-ray crystal structure analysis. Most compounds from this series not only show sub-nanomolar IC(50) values for CDK2, but also demonstrate almost 1000-fold selectivity to other kinases including CDK1.

MeSH terms

  • Binding Sites
  • CDC2-CDC28 Kinases / antagonists & inhibitors*
  • CDC2-CDC28 Kinases / chemistry
  • Crystallography, X-Ray*
  • Cyclin-Dependent Kinase 2
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Protein Binding
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Pyrazoles
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2