Design, synthesis and characterization of N9/N7-substituted 6-aminopurines as VEGF-R and EGF-R inhibitors

In this study we report on the design, synthesis and biological characterization of novel N9 or N7 arylethanone-substituted 6-aminopurines and 6-methoxypurines, respectively, as EGF-R and VEGF-R inhibitors. The compounds were initially profiled in a panel of 24 cancer-relevant protein kinases. Dependent on the regio-substitution of the purine core we found inhibition activity for EGF-R and VEGF-R with IC50 values in the μM range. The two novel N9/N7 2-(6-amino-purine)-1-(1H-indole-3-yl)ethanone derivatives were characterized in an enhanced panel of 78 kinases showing the N9 derivative to also inhibit MNK1 and IRR while the N7 isomer was found to be specific for VEGF-R2.

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