Synthesis of 1-[4-(m-tolyl)amino-6-quinazolinyl]3-[14C]-methyl triazene:: a radiolabeled probe for the combi-targeting concept

The synthesis of 1-[4-(m-tolyl)amino-6-quinazolinyl]-3-[C-14]-methyl triazene (SMA41) is described. This triazene was designed to be hydrolyzed under physiological conditions to N-4-m-tolyl-quinazoline-4,6-diamine (SMA52), a moderate inhibitor of the epidermal growth factor receptor (EGFR) and the DNA alkylating species [C-14]-methyldiazonium. A radiolabeled probe was needed to test the hypothesis that in situ hydrolysis of SMA41 may induce alkylation of the ATP binding site of EGFR. C-14-SMA41 was obtained with a radiochemical yield of 21% and a specific activity of 54.6 mCi/mmol, as determined by HPLC quantitation and scintillation counting. Radio-TLC analyses showed 98% radiochemical purity. Copyright (C) 2003 John Wiley Sons, Ltd.