Allene as an Alternative Functional Group for Drug Design: Effect of CC Multiple Bonds Conjugated with Quinazolines on the Inhibition of EGFR Tyrosine Kinase

A series of allenic quinazolines were synthesized as receptor tyrosine kinase inhibitors by using a simple protocol for palladium‐catalyzed allene transformation. Among the compounds synthesized, two allenic 4‐anilinoquinazolines selectively suppressed epidermal growth factor receptor (EGFR) tyrosine kinase activity in vitro. According to immunoblot analysis, the allenic quinazolines inhibited the EGF‐mediated phosphorylation of EGFR and its downstream kinases in A431 cells. Furthermore, one of these allenic quinazolines decreased the proliferation of A431 cells through the induction of cell‐cycle arrest and apoptosis. Are allenes attractive functional groups for drug design? A series of allenic 4‐anilino‐ and 4‐phenoxyquinazolines were synthesized and evaluated. Among the compounds synthesized, the allenic quinazoline 1 a inhibits EGF‐mediated phosphorylation of EGFR and its downstream kinases in A431 cells, which results in cell‐cycle arrest and apoptosis.