Structural modifications at the pyrimidine ring and at the C9, N'O-bridge region of the thymidylate synthase (TS) inhibitors@ o-propargyl-5, sdideezafolate (1; PDDF CB 3717), 2 d~ o-IP o-pr 5,~~ d~ o~ te(2, DPDDF), and 2-desamino-2-methyl-IPo-propargyl-5, 8- dideazafolate (3, DMPDDF) have been carried out. Methods for the synthesis of 2-desamino- @ o-propargyl-1, 5, 8-tridedolate (41, 2-desamino-2-methyl-IPo-propargyl-3, 5, 8- ...