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

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 in vitro. The most promising compound 51, of which the IC50 values were 0.66 mu M, 0.38 mu M and 0.44 mu M 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 R-3 = 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. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

A series of novel compounds were synthesized and tested for their moderate to excellent activity against cancer cell lines in vitro. One of the compounds showed promising potential to be a candidate for the development of anti-tumor drugs, with better activity and apoptosis effect than the positive control. Further research on this compound included c-Met kinase activity and selectivity, concentration dependence, and molecular docking.