152 



PTEROYLGLUTAMIC ACID 



Biirchenal et «i."^ studied the action of six purines against Ak4 leukemia in 

 mice and found 'i.fi-diaminopurine effective. The corresponding methyl 

 derivative, 2,6-diamino-7-methylpurine, was ineffective. 



3. Pteridine Derivatives 



A large series of 2,4-diaminopteridines and 2-amino-4-hydroxypteridines 

 have been prepared^^ and their biological effects studied. 



TABLE VI 

 Antagonistic Action of Substituted Pteridines 



Inhibition Index 



Compound 



2,4-Diaminopteridine 

 2 , 4-Diamino-7-methylpteridine 

 2,4-Diamino-6,7-dimethylpteridine 

 2,4-Diamino-6,7-dicarboxypteridine 

 2,4-Diamino-6,7-diphenylpteridine 

 2, 4-Diamino-6,7-phenanthro- (9, 10-e) -pteri- 

 dine 

 2-Amino-4-hydroxy-6 , 7-diphenylpteridine 



40,000 



200,000 



68 



H< 



H 



6 



N 



N 

 3N 



NH2 



NH2 



2,4-Diaminopteridine 

 (related to 4- amino- 

 pterojdglutamic acid) 





N N 



\ 



N 



-NH, 



N 



OH 



2-Amino-4-hydroxy- 



pteridine (related 



to pteroylglutamic acid) 



The microbiological effects of some of these are shown in Table VI. One 

 interesting fact which is apparent from this data is the much higher ac- 

 tivity of the inhibitors for *S. faecalis than for L. casei. Thus 2,4-diamino- 

 6, 7-diphenylpteridine has an inhibition index (ratio of antagonist to 

 metabolite) of 8 for S. faecalis and 100,000 for L. casei. However, when the 

 2,4-diaminopteridine is incorporated into the PGA molecule to give 

 4-aminopteroylglutamic acid, the inhibition index for the two organisms is 

 approximately the same (Swendseid^^). The inhibitory activity of the 

 2,4-diaminopteridines increases as the size of the substitution groups in- 



6' C. K. Cain, M. F. Mallette, and E. C. Taylor, Jr., /. A171. Chem. Soc. 70, 3026 



(1948). 

 68 M. E. Swendseid, E. L. Wittle, G. W. Moersch, O. D. Bird, and R. A. Brown, J. 



Biol. Chem. 179, 1175 (1949). 



