Synthesis of AX7593, a Quinazoline-Derived Photoaffinity Probe for EGFR

The synthesis of a photoaffinity probe for EGFR is described. O-Alkylation of 4-(<i>meta</i>-azidoanilino)-6-methoxy-7-hydroxy-quinazoline with a protected tetraethyleneglycol linker followed by the attachment of tetramethylrhodamine yielded the fluorescent probe AX7593. Photoaffinity labeling of EGFR by <b>AX7593</b> (<i>K</i><sub>b</sub> = 280 nM) was shown to have an efficiency of 34% and to be competitive with the EGFR inhibitors PP2 and AG1478.