A study of the metabolism of 2,4-diaminopyrimidine.

Recent studies have revealed that various derivatives of 2,4-diaminopyrimidine exhibit profound biochemical reactivity. For example, nearly all 2,4-diaminopyrimidines and their condensed ring systems inhibit the growth of LactobaciZZus casei with folic acid (1). 2,4-Diamino&p-chlorophenoxypyrimidine was found to be a potent antimalarial in that it was active against Plasmodium gallinaceum infection in chicks (2) ; the activity exhibited was of the same order as that of quinine. A definite chemotherapeutic effect of 2,6-diaminopurine’ and 4-amino-iV”-methylfolic acid against transplanted mouse leucemia has been described (3, 4). Inhibition by 2,6-diaminopurine of the multiplication of vaccinia virus in vitro (5) and of estrogen-induced growth in the genital tract of the female chick has been observed (6). In addition, this purine, 2,6-diaminopurine, was found to be utilized by the rat for nucleic acid guanine synthesis (7, 8). It was therefore felt desirable to investigate the metabolic fate of the simplest member of this series and this communication will deal with a metabolic study of 2,4-diaminopyrimidine’ and a report on its ri?le in the biosynthesis of nucleic acids. The pyrimidines occurring naturally in nucleic acids, uracil (9), thymine (9), and cytosine (lo), have been found to be inactive in this regard. On the other hand, erotic acid (4-carboxyuracil) is an active precursor of nucleic acid pyrimidines (11). When rats on an otherwise normal diet were permitted to ingest 2,4diaminopyrimidine (12), labeled with an excess of N16 in the land 3nitrogen atoms as well as in the 2-amino group, the compound was extensively absorbed, as evidenced by the rather high N16 content of the urine (Table I). No evidence of incorporation into the tissue nucleic