A pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGFR protein tyrosine kinase and a putative binding mode of 4-anilinoquinazoline suggest that a salicylic acid function could serve as the pharmacophore replacement of a pyrimidine ring. Superpositions by CAMM of salicylanilides with the potent EGFR tyrosine kinase inhibitor 4-[(3'-chlorophenyl)amino]-6,7-dimethoxyquinazoline showed that salicylanilides should act as tyrosine kinase inhibitors. A series of salicylanilides was synthesized and their inhibitory activity against tyrosine kinases determined. Some of them indeed proved to be potent and selective EGFR tyrosine kinase inhibitors. The most potent ones being 28, 16, 20, 6, and 15, with IC(50) in the 23-71 nM range.