Abstract Three derivatives of 2-amino-6-methyl-5-(p-tolylsulfonamidopropyl)-4-pyrimidinol (I) with N-substituents on the sulfonamide group, namely bromoacetamidopropyl (XVI), m- bromoacetamidobenzyl (XXIVa), and p-bromoacetamidobenzyl (XXIVb), were synthesized as candidate active-site-directed irreversible inhibitors of thymidylate synthetase. The bromoacetamidopropyl derivative,(XVI), the p-bromoacetamidobenzyl derivative (XXIVb), ...