| Abstract
| - The epidermal growth factor receptor (EGFR), a long-standing drug development target, isalso a desirable target for imaging. Sixteen dialkoxyquinazoline analogues, suitable for labelingwith positron-emitting isotopes, have been synthesized and evaluated in a battery of in vitroassays to ascertain their chemical and biological properties. These characteristics providedthe basis for the adoption of a selection schema to identify lead molecules for labeling and invivo evaluation. A new EGFR tyrosine kinase radiometric binding assay revealed that all ofthe compounds possessed suitable affinity (IC50 = 0.4−51 nM) for the EGFR tyrosine kinase.All of the analogues inhibited ligand-induced EGFR tyrosine phosphorylation (IC50 = 0.8−20nM). The HPLC-estimated octanol/water partition coefficients ranged from 2 to 5.5. Fourcompounds, 4-(2‘-fluoroanilino)- and 4-(3‘-fluoroanilino)-6,7-diethoxyquinazoline as well as 4-(3‘-chloroanilino)- and 4-(3'-bromoanilino)-6,7-dimethoxyquinazoline, possess the best combinationof characteristics that warrant radioisotope labeling and further evaluation in tumor-bearingmice.
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