Versatile templates for the development of novel kinase inhibitors: Discovery of novel CDK inhibitors

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6216-9. doi: 10.1016/j.bmcl.2007.09.018. Epub 2007 Sep 8.

Abstract

A series of four bicyclic cores were prepared and evaluated as cyclin-dependent kinase-2 (CDK2) inhibitors. From the in-vitro and cell-based analysis, the pyrazolo[1,5-a]pyrimidine core (represented by 9) emerged as the superior core for further elaboration in the identification of novel CDK2 inhibitors.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinase 2 / chemistry
  • Cyclin-Dependent Kinase 2 / drug effects*
  • Cyclin-Dependent Kinase Inhibitor Proteins / chemical synthesis
  • Cyclin-Dependent Kinase Inhibitor Proteins / chemistry*
  • Cyclin-Dependent Kinase Inhibitor Proteins / pharmacology*
  • Drug Design
  • Inhibitory Concentration 50
  • Molecular Structure
  • Protein Binding
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*

Substances

  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • pyrazolo(1,5-a)pyrimidine
  • Cyclin-Dependent Kinase 2