Discovery of a novel class of 2-aminopyrimidines as CDK1 and CDK2 inhibitors

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4203-5. doi: 10.1016/j.bmcl.2011.05.081. Epub 2011 May 27.

Abstract

A series of new 2-(2-aminopyrimidin-4-yl)phenol derivatives were synthesized as potential antitumor compounds. Substitution with pyrrolidine-3,4-diol at the 4-position of phenol provided potent inhibitory activity against CDK1 and CDK2. X-ray crystal structural studies were performed to account for the effect of the substituent on both the enzymatic and cell growth inhibitory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Binding Sites
  • CDC2 Protein Kinase / antagonists & inhibitors*
  • CDC2 Protein Kinase / metabolism
  • Cell Line, Tumor
  • Computer Simulation
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 2 / metabolism
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Humans
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / toxicity
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / toxicity

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrimidines
  • 2-aminopyrimidine
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinase 2