BIOCHEMICAL ANTAGONISM 



this group belong glucoascorbic acid, a-locophcrol quinone, and des- 

 thiobiotin, to mention only a few prominent members. 



At the present very early stage of our knowledge, there arc 

 many questions demanding answers; and for many of these adequate 

 ones are not yet available. Let us examine two. From the examples 

 now at hand it appears that the exchange of carbon atoms for nitrogen 

 in six-membered rings leads to the production of inhibitory com- 

 pounds. Witness the effectiveness of conversion of pyrimidine de- 

 rivatives to benzene compounds. It would be well to know whether 

 the process is unilateral, that is, whether the exchange of nitrogen for 

 carbon would be equally as successful as the reverse process. From 

 the cases of iodinin, and of benzimidazole and triazolopyrimidine (see 

 next paragraph), and from the fact that 6-aminonicotinic acid behaves 

 competitively with /?-aminobenzoic acid, it would seem that the 

 process actually is not unilateral. 



Take now the question of how great the change in structure 

 must be to attain maximal activity in the inhibitory analogue. Is it 

 preferable to make as small a change as possible, and if so, what is the 

 measure of the sizfe of the change which is made? If one examines a 

 case in which progressive change has been made it would seem that a 

 small alteration is better than a larger one, but this cannot be stated 

 with any assurance because of the lack of a standard of magnitude of 

 change. Benzimidazole is derived from the purines, adenine and 

 guanine, by elimination of the nuclear substituents, and by exchange 

 of the two pyrimidine nitrogen atoms for carbon. It is less active in 

 the inhibition of bacterial growth than are the triazolopyrimidines, 

 which differ from the purines only in that the imidazole carbon of the 

 latter has been replaced by a nitrogen atom. Thus, the exchange of 

 one carbon atom for a nitrogen gives a more potent compound than 

 was obtained by trading two nitrogen for two carbon atoms. 



Of course, the two exchanges are not strictly comparable because in 

 one case the imidazole ring is altered and in the other the pyrimidine part is 

 transformed. It will be necessary to examine the activity of pyridinoimidazole 

 and its amino and hydroxy derivatives before unequivocal conclusions may be 

 made about the matter. A more unambiguous illustration deals with deriva- 

 tives of /?-aminobenzoic acid. Replacement of one carbon atom with nitrogen 

 yields 6-aminonicotinic acid which is antagonistic, while exchange of two 

 carbon for two nitrogen atoms to form 2-amino-5-carboxypyrimidine gives 



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