Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidine derivatives containing 1,8-naphthyridine-4-one fragment.

Abstract

In this study, a series of pyrrolo [2,3-d]pyrimidine derivatives containing 1,8-naphthyridine-4-one fragment were synthesized and their biological activity were tested. Most of the target compounds displayed moderate to excellent activity against one or more cancer cell lines and low activity against human normal cell LO2 invitro. The most promising compound 51, of which the IC50 values were 0.66μM, 0.38μM and 0.44μM against cell lines A549, Hela and MCF-7, shown more remarkable activity and better apoptosis effect than the positive control Cabozantinib. The structure-activity relationships (SARs) indicated that double-EWGs (such as R3=2-Cl-4-CF3) on the terminal phenyl rings was a key factor in improving the biological activity. In addition, the further research on compound 51 mainly included c-Met kinase activity and selectivity, concentration dependence, and molecular docking.