Synthesis, structure, and biological assay of cinnamic amides as potential EGFR kinase inhibitors

A series of derivatives of cinnamic amide (compounds 2a – 2v ) were synthesized and evaluated for antiproliferative activities against the human breast cancer cell line MCF-7- and EGFR-inhibitory activities. The structures of compounds 2b and 2i were determined by single-crystal X-ray diffraction analysis. Compounds 2f and 2j showed moderate EGFR inhibitory activity with IC 50 values of 5.16 and 7.37 μM, respectively. Docking simulation of compound 2f was carried out to illustrate the binding mode of the molecule into the EGFR active site. Structure–activity relationship analysis found that the N -phenyl rings are required for enhancing the activities.