V. SPECIFICITY OF ACTION 



151 



II, N 



HoN NHo 



N 



O- 



Cl 



Cl 



2, l-Diainino-S-iu-flilorophonoxy 

 pyrimidiiie 



The action of 2,4-cliamino-5-p-chloropheiioxyp3a-imidine was found to 

 inhibit the growth of L. casei at levels of 0.5 7 per milliUter and to be com- 

 petitively reversed bj^ PGA. Paludrine produced partial growth inhibition 

 at levels of 100 7 per milliliter which could be reversed by PCiA. Higher 

 le\'els of paludrine which produced complete growth inhibition could not 

 be reversed by an e.xcess of PGA. The 2,4-diamino-5-p-chlorophenoxy- 

 pyrimidine was found to be as effective as quinine against Plasmodium 

 yallinaceum.^^ 



Burchenal et al.^^ found twenty-three pyrimidine analogs to be ineffective 

 against transmitted leukemia Ak4 in mice. 



2. Purine Derivatives 



Purines with amino groups in the 2,6-positions have been found to be 

 l)otent PGA antagonists (Elion and Hitchings''^). The 2,G-positions of the 

 purine correspond to the 2,4-positions of pyrimidines and pteridines. 



N 



N 



I 

 NH2 



2,4-Diamino- 

 pyrimidine 



HCs 



/N9 



N 



iN 



NHo 



2,6-Diamin()purine 



2,()-r)iaminopurine inhibits growth of L. casei at a level of 0.1 7 per 

 milliliter. Pteroylglutamic acid is capable of reversing the growth inhibition 

 produced by low levels of this compound but not that produced by high 

 levels. Adenine is also capable of reversing the antagonist at low levels of 

 the inhibitor. In contrast, the inhibitory action of 2-aminopurine is reversed 

 by either PGA or purines over a considerable range of concentration. 



^'■'.J. R. Burchenal, S. F. Johnston, J. R. Burchenal, M. N. Kushida, E. Robinson, 

 and C. C. Stock, Proc. Soc. Exptl. Biol. Med. 71, 381 (1949). 



