D. W. WOOLLEY 



were so large as to make its clinical application impractical. It is 

 possible that useful agents against infectious diseases may be produced 

 by investigation of inhibitory analogues, but at present this has not 

 been done. Meanwhile, it is well to remember that anti-infection 

 agents form only a part of the chemotherapeutic arsenal, and that 

 magic bullets against noninfectious diseases as well as against infections 

 may eventually be cast in the mold before us. 



The third new aspect to be considered is an outgrowth of the 

 previous two general aspects. If it is possible to evoke the various 

 types of manifestations discussed, then it is well to examine the classes 

 of structural changes that must be made in a metabolite molecule in 

 order that it may exhibit inhibitory action. At the present time, two 

 general types of structural change which bring about this result can 

 be seen. In addition, there is a third group of structural alterations 

 about which it is not yet possible to make generalizations. 



The first general type of structural change involves the replace- 

 ment of the carboxyl group of acidic metabolites by some other group. 

 The most frequently studied exchange has been that of sulfonic acid or 

 amide for the carboxyl. Examples of this class are: sulfanilamide and 

 its derivatives which are related to /^-aminobenzoic acid; S-pyridinc- 

 sulfonic acid, related to nicotinic acid; the a-aminosulfonic acids, 

 related to the a-aminocarboxylic acids; and thiopanic acid, related 

 to pantothenic acid. With the possible exception of 3-pyridine- 

 sulfonic acid, members of this class of inhibitors are not effective in 

 the production of deficiencies in animals. Furthermore, it is from this 

 class that many useful agents against infectious diseases, that is, the 

 sulfonamides and thiopanic acid, have come. Possibly the inactivity 

 toward animals contributes to their chemotherapeutic effectiveness, 

 for it may result in damage to the invading microorganisms without 

 causing undue violence to the host. 



Inhibitory analogues have also been produced by replacement 

 of — COOH by — COR, but the class of compounds so derived has 

 not been studied as intensively as that just examined. Thus sub- 

 stitution of the — COOH of j&-aminobenzoic acid by — COCH3 (to 

 yield /'-aminoacetophenone) led to the formation of a bacteriostatic 

 substance whose action was reversible by /?-aminobenzoic acid. A 

 related ketone protected mice against experimental infections. Simi- 

 larly the exchange of — COOH in nicotinic acid for — COCH3 to 



