Design, Synthesis, and Antitumor Activity of D‐13 Derivatives

ABSTRACT In this paper, a series of benzopyrimidine derivatives were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. The cytotoxicity of these compounds against a variety of cells, including MDA‐MB‐231 (breast cancer) and HeLa (cervical cancer), was assessed by MTT. The majority of benzopyrimidine derivatives have been found to exhibit superior antitumor activity in comparison with D‐13. Compound 12f showed the most potent antiproliferation activity on the MDA‐MB‐231 cell line. Its IC 50 value was 3. 04 ± 0.13 µM, which was significantly lower than that of D‐13 (8.68 ± 0.13 µM) and Pomalidomide (389.47 ± 35.83 µM). Further research on the antitumor activity of Compound 12f revealed the efficacy of Compound 12f in inhibiting the proliferation, migration, adhesion of tumor cells and the growth of cell xenotransplantation with MDA‐MB‐231 cells. The Chai‐1 prediction indicates that compound 12f mediates the formation of a stable, structurally complementary ternary complex between CRBN and DCAF1, establishing a structural basis for efficient DCAF1 degradation.