Design, synthesis and molecular docking analysis of some novel 7-[(quinolin-6-yl)methyl] purines as potential c-Met inhibitors

HGF/c-Met signaling pathway has come into the spotlight as a promising therapeutic target for inhibiting tumor growth and has become one of the leading molecular targets in cancer. Various strategies are currently in development to disrupt the HGF–Met signal transduction pathway, in which small molecular inhibitors have been a particularly active field. On the basis of the structures of two c-Met inhibitors, PF-04217903 and JNJ-38877605, some novel 7-[(quinolin-6-yl)methyl] purines ( 4a – 4e ) were rationally designed on the principle of bioisosterism strategy. These compounds were synthesized and evaluated as novel c-Met inhibitors. Molecular docking experiments analyzed the results and explained the molecular mechanism of eminent activities to c-Met. The results showed that all the title compounds were active against c-Met enzyme to some extent. Though these compounds did not demonstrate inhibition as we expected, this study provided important information for building diversification of chemical library and molecular docking experiment supplied the basis for further research works. Graphical Abstract Some novel 7-[(quinolin-6-yl)methyl] purines as potential c-Met inhibitors have been designed and prepared. Their synthesis and spectral characterization are reported here.