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

摘要

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 IC50 values ranging from 0.089 to 5.46 μM. Especially, compound >5a exhibited the most active potency both in cellular (IC50 = 0.15, 0.089, 0.36, and 0.75 μM, respectively) and enzymatic assay (IC50 = 56 nM against EGFR), representing a promising lead for further optimization.