Imidazo[1,2-a]pyridines: a potent and selective class of cyclin-dependent kinase inhibitors identified through structure-based hybridisation

Bioorg Med Chem Lett. 2003 Sep 15;13(18):3021-6. doi: 10.1016/s0960-894x(03)00638-3.

Abstract

High-throughput screening identified the imidazo[1,2-a]pyridine and bisanilinopyrimidine series as inhibitors of the cyclin-dependent kinase CDK4. Comparison of their experimentally-determined binding modes and emerging structure-activity trends led to the development of potent and selective imidazo[1,2-a]pyridine inhibitors for CDK4 and in particular CDK2.

MeSH terms

  • CDC2-CDC28 Kinases / antagonists & inhibitors
  • CDC2-CDC28 Kinases / chemistry
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / chemistry
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Protein Binding
  • Proto-Oncogene Proteins*
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Pyridines
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases