Synthesis, biological evaluation and docking studies of new pyrrolo[2,3-d] pyrimidine derivatives as Src family-selective tyrosine kinase inhibitors

J Enzyme Inhib Med Chem. 2013 Oct;28(5):1080-7. doi: 10.3109/14756366.2012.715288. Epub 2012 Sep 7.

Abstract

In this study, the synthesis and potential enzyme interactions of new Pyrrolo[2,3-d]pyrimidine derivatives along with their inhibitory activity against SFK enzymes such as Fyn, Lyn, Hck, and c-Src were reported. The results indicated that compounds were slightly active of tested SFK enzymes in comparison with PP2 for Fyn, A-419259 for Lyn and CGP77675 for c-Src. Compound N-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)-4-(3,4-dimethoxyphenyl)butanamide (5) was identified as a non-selective slight inhibitor against Fyn, Lyn and c-Src. However, compounds did not show any inhibitory effects on Hck. Docking studies were performed to analyze the binding mode of compounds against SFKs. The best interaction was obtained between compound 5 and the active site of Fyn and c-Src enzymes in comparison with reference compounds PP2 and CGP77675, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Structure-Activity Relationship
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / metabolism

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Pyrrolo(2,3-d)pyrimidine
  • src-Family Kinases