Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5027-30. doi: 10.1016/j.bmcl.2010.07.045. Epub 2010 Jul 15.

Abstract

Pyrrolidine, pyrrolidinone, carbocyclic, and acyclic groups were used as isosteric proline replacements in a series of insulin-like growth factor I receptor kinase/insulin receptor kinase inhibitors. Examples that were similar in potency to proline-containing reference compounds were shown to project a key fluoropyridine amide into a common space, while less potent compounds were not able to do so for reasons of stereochemistry or structural rigidity.

MeSH terms

  • Models, Molecular
  • Proline / chemistry*
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, Insulin / antagonists & inhibitors*
  • Triazines / chemistry*
  • Triazines / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Triazines
  • Proline
  • Receptor, IGF Type 1
  • Receptor, Insulin