Fused Imidazo[1,2-a]pyrimidines Containing 1,2,3-Triazoles and Isoxazoles: One-Pot Synthesis, Anticancer, and EGFR-Inhibitory Activities
摘要
Objective: A series of imidazo[1,2-a]pyrimidine derivatives containing 1,2,3-triazoles and isoxazoles were synthesized, and their anticancer activity against lung cancer was evaluated. Methods: The one-pot reaction of (Z)-N-(4-iodobut-3-yn-2-ylidene)-1H-imidazol-2-amine III with various nitrile oxides and aryl azides, proceeding via in situ generated 4-iodoisoxazoles and 5-iodotriazoles, yielded the final fused isoxazoles and triazoles. The anticancer activity of the synthesized derivatives was determined using the MTT assay. Results and Discussion: The structures of the newly synthesized compounds were confirmed by 1H, 13C NMR, and mass spectrometry. Among the derivatives, compounds IVe and IVd exhibited potent activity against the A549 cell line with IC50 values of 4.43 ± 0.36 and 6.52 ± 0.63 μM, respectively. They also demonstrated significant EGFR inhibitory activity with IC50 values of 0.67 ± 0.05 and 0.89 ± 0.07 μM, respectively. Conclusions: A new series of fused imidazo[1,2-a]pyrimidines containing 1,2,3-triazoles and isoxazoles was developed and investigated for in vitro activity against lung cancer. Compounds IVe and IVd showed promising results in both cytotoxicity and EGFR inhibition assays. These scaffolds, with further structural optimization, hold potential as candidates for future cancer therapeutics.