THE CHEMISTRY OF DDATHF (5,10-DIDEAZA-5,6,7,8-TETRAHYDROFOLIC ACID) AS ANTITUMOR AGENT

Over the past 40 years, big efforts have been devoted to the developme nt of novel folate antimetabolites. All of the potent antifolates have reportedly been inhibitors of dihydrofolate reductase (DHFR). In 1985 , Taylor and et al. reported the synthesis of 5,10-dideaza-5,6,7,8-tet rahydrofolic acid, DDATHF, which exhibits broad and selective antitumo r activity as an inhibitor of glycinamide ribonucleotide formyltransfe rase (GARFT). DDATHF is a close analog of tetrahydrofolic acid, differ s only by replacement of the 5- and 10- position nitrogen atoms by car bon. It may exist in two diastereomeric forms, differing in configurat ion at carbon 6. Both diastereomers of DDATHF are potent inhibitors of cell growth in culture. DDATHF is currently in Phase II clinical tria ls.