Synthesis and biological activity of 5-[(2,5-dihydroxybenzyl)amino]salicylic acid analogs as inhibitors of EGF receptor-associated protein tyrosine kinase

The synthesis and biological activity of a series of 5-[(2,5-dihydroxybenzyl)amino]salicylic acid derivatives (3–6) as analogs of the active partial structure (2) of the potent EGF-R tyrosine kinase inhibitor lavendustin A (1) are described. Analogs with an electron-withdrawing group in place of the carboxyl group of 2 showed activity. The N-hexylsalicylamide analog 6b (IC50=0.9 μM) was about four times more potent than 2.