Synthesis and cytotoxic activity of imatinib derivatives

Abstract

Fourteen derivatives of imatinib have been prepared by condensation of (L)-N-acylation amino acid with N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidine amine (6), which was prepared from 3-acetyl-pyrimidin and 2-methyl-5-nitroaniline through the reactions of addition, condensation, cyclization and reduction, respectively. The structures of all target compounds were characterized by IR, 1H NMR, 13C NMR and HRMS techniques. They were evaluated for cytotoxic activity against human Leukemia cells (K562), human non-small-cell-lung cancer cells lines (A549) and human hepatoma cell lines (HepG-2) by methyl thiazolyl tetrazolium (MTT) method. The results showed the cytotoxic activities of compounds 7d,7i,7j,7k,7l, 7n against human Leukemia cells (K562) and human non-small-cell-lung cancer cell lines (A549), compounds 7a, 7d,7e against human hepatoma cell lines (HepG-2) were comparable to those of imatinib.