The Design, Synthesis And Biological Activity Study Of Dasatinib Derivatives

Anti-tumor drug research has been a great breakthrough in recent years,Anti-cancer drugs have also been more and more attention. People put a high value on dasatinib because of its unique anti-tumor activity and action. The treatment of leukemia plays a significant role. However, dasatinib has its drawbacks: low bioavailability, myelosuppression (thrombocytopenia, neutropenia and anemia),bleeding, fluid retention, etc, so the structure of dasatinib is modified in the future research direction.In this paper, the synthesis route of dasatinib was optimized, which could provide intermediates and synthesis methods for the synthesis of dasatinib derivatives.Based on the synthesis of dasatinib and the principle of drug conjugation, we modified some dasatinib groups, synthesized 26 new compounds, and characterized their structures. The bioactivity of the new compounds was determined by MTT method. The biological activities of the new compounds 9a, 9g, 9k, 9p, 1lf were good,and their IC50 values were all less than 1?mol/L. The new compound 9a had the best bioactivity, and its IC50 was 0.27?mol/L. The IC50 of compound 91, 9m and 11b were between 1?2?mol/L,and the structure-activity relationship was analyzed.