<scp> Cs ₂ CO ₃ </scp> ‐Promoted Synthesis of Guanidinobispyrimidine Derivatives as Potential Breast Cancer Cell Inhibitors

ABSTRACT In this work, one facile approach for the synthesis of guanidinobispyrimidine derivatives promoted by Cs 2 CO 3 was reported, delivering 22 new compounds ( 3a – 3v ) in moderate to good yield (62%–88% yield). Afterwards, the plausible reaction pathway, including two nucleophilic processes, was proposed based on the capture of possible intermediate A 1 . Furthermore, biological activity evaluation revealed that most of these newly prepared guanidinobispyrimidines, including compounds 3g , 3o , 3r , and 3 s , can strongly inhibit the growth of MCF‐7 (human breast cancer cell line) with IC 50 value ranging from 0.81 to 8.02 μM, which is comparable to natural product lycorine (IC 50 = 3.7 μM). Among them, compound 3g exhibited the best inhibitory activity against MCF‐7 with IC 50 value of 0.81 ± 0.21 μM. Meanwhile, these guanidinobispyrimidines also exhibited good safety to normal cells, including MCF‐10A (normal human breast epithelial cells) and SH‐SY5Y (human neuroblastoma cell line). All these results demonstrate the enormous application potential of this newly developed approach in the development of new breast cancer cell inhibitors in the future.