Abstract Five previously undescribed trimetrexate analogues with bulky 2′-bromo substitution on the phenyl ring were synthesized in order to assess the effect of this structure modification on dihydrofolate reductase inhibition. Condensation of 2-[2-(2-bromo-3, 4, 5- trimethoxyphenyl) ethyl]-1, l-dicyanopropene with sulfur in the presence of N, N- diethylamine afforded 2-amino-5-(2′-bromo-3′, 4′, 5′-trimethoxybenzyl)-4-methyl- ...
