Novel oxazolo[4,5-g]quinazolin-2(1H)-ones: dual inhibitors of EGFR and Src protein tyrosine kinases.

Quinazoline-containing derivatives are an important class of synthetic products and represent an attractive scaffold for EGFR inhibitors. A series of oxazolo[4,5-g]quinazolin-2(1H)-one derivatives were synthesized and the EGFR and Src inhibition activities were evaluated using Gefitinib as lead compound. The three most potent compounds 5y, 5l and 5a each inhibited EGFR at the IC(50) value of 61 nM, 67 nM and 78 nM. Among them, 5c also demonstrated excellent inhibition activity against Src with the IC(50) value of 3.1 μM. Several of these derivatives also showed good anti-proliferation effects against KB and A498 cells.