The 5, 6, 7&tetrahydro derivative (I) of the powerful thymidylate synthase inhibitor~ 0- propargyl-5, 8-dideazafolic acid (PDDF) has been synthesized and evaluated for its antifolate activity. A convenient method for the preparation of the key intermediate 2-amino-6- (bromomethyl)-4-hydroxy-5, 6, 7, 8-tetrahydroquinazoline (18) is described. Two closely related analogues of 1 were also synthesized and evaluated for their antifolate activity and ...