Synthesis of AX7593, a quinazoline-derived photoaffinity probe for EGFR

Abstract

(Chemical Equation Presented) The synthesis of a photoaffinity probe for EGFR is described. O-Alkylation of 4-(meta-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 AX7593 (Kb = 280 nM) was shown to have an efficiency of 34% and to be competitive with the EGFR inhibitors PP2 and AG1478.