Discovery of novel Purine derivatives with potent and selective inhibitory activity against c-Src tyrosine kinase

He Huang, Jingui Ma, Jianmei Shi Linghua Meng Hualiang Jiang, Jian Ding, and Hong Liu

We report here the discovery of novel purine derivatives with potent and selective inhibitory activity
against c-Src tyrosine kinase by adopting a strategy integrating focused combinatorial library design, virtual
screening, chemical synthesis, and bioassay. Thirty two compounds were selected and synthesized.
All compounds showed potent inhibitory activity against c-Src kinase with IC50 values ranging from
3.14 lM to 0.02 lM. Compound 5i was identified as one of the most potent agent with an IC50 120 times
lower than those of the hits. The high hit rate (100%) and the potency of the new Src kinase inhibitors
demonstrated the efficiency of the strategy for the focused library design and virtual screening. The novel
active chemical entities reported here should be good leads for further development of purine-based anticancer
drugs targeting Src tyrosine kinase.