Synthesis, 11C labeling and biological properties of derivatives of the tyrphostin AG957

Abstract

Four analogues of AG957, a known inhibitor of the tyrosine kinase p210 bcr-abl, have been synthesized and tested for their growth inhibitory effect against the BCR/ABL-positive FDrv210C cells as well as the epidermal growth factor (EGF) receptor-positive Baf/ERX cells. All compounds that can undergo oxidation to the corresponding quinone demonstrated inhibition of FDrv210C cells and Baf/ERX cells. Compounds that cannot become oxidized showed significantly less inhibition of BCR/ABL- or EGF receptor-mediated cell proliferation. The 11C-labeled compounds were prepared by labeling 4-aminobenzoic acid using [11C]CH3I, which afforded the corresponding 11C-labeled methyl ester in excellent yields...