Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors

Two novel series of diaryl urea derivatives 5a–i and 13a–l were synthesized and evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231 cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives 5a–i demonstrated significant activity, and seven of them are more active than sorafenib, with IC(50) values ranging from 0.089 to 5.46 μM. Especially, compound 5a exhibited the most active potency both in cellular (IC(50) = 0.15, 0.089, 0.36, and 0.75 μM, respectively) and enzymatic assay (IC(50) = 56 nM against EGFR), representing a promising lead for further optimization.