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

摘要

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.