Structure-based design of a new class of highly selective aminoimidazo[1,2-a]pyridine-based inhibitors of cyclin dependent kinases

Bioorg Med Chem Lett. 2005 Apr 1;15(7):1943-7. doi: 10.1016/j.bmcl.2005.01.052.


Structure-based design approach was successfully used to guide the evolution of imidazopyridine scaffold yielding new structural class of highly selective inhibitors of cyclin dependent kinases that were able to form a new interaction with an identified residue of the protein, Lys89. Compounds from this series have shown no detectable effect when tested against a representative set of other serine/threonine kinases such as GSK3beta, CAMKII, PKA, PKC-alpha,beta,epsilon,gamma. Compound 2i inhibits proliferation in HCT 116 cells in tissue culture. Synthesis, co-crystal structure of CDK2 in complex with compound 2i, and preliminary SAR study are disclosed.

MeSH terms

  • Cells, Cultured
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • HCT116 Cells
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Inhibitory Concentration 50
  • Lysine / chemistry
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Imidazoles
  • Protein Kinase Inhibitors
  • Pyridines
  • Cyclin-Dependent Kinases
  • Lysine