p-AMINOBENZOIC ACID 493 



cally active forms of folic acid by Streptobacterium plantarum. 87 Synthesis 

 of this factor is inhibited by either sulfanilamide or sulfathiazole, and 

 the inhibition is prevented competitively by p-aminobenzoic acid. 87 The 

 synthesis of the folic acid group by yeast is also inhibited by sulfona- 

 mides. ss 



The utilization of pteroic acid by Streptococcus faecalis R, which 

 requires folic acid for growth, is not inhibited by sulfonamides. 71 



Pteroyl-di-y-glutamylglutamic acid has an action similar to that of 

 folic acid for organisms which utilize either p-aminobenzoic acid or folic 

 acid (Table 3). The action of sulfonamides on such organisms is non- 

 competitively reversed by the triglutamate at a concentration somewhat 

 higher than that of folic acid essential for a similar response. 



Inhibitory Analogues of p-Aminobenzoic Acid 



After the discovery of the therapeutic activity of sulfanilamide, 8 a 

 tremendous number of analogous compounds were prepared and tested 

 as possible chemotherapeutic agents. Actually, many of the more efficient 

 sulfonamides known today were in common use before the discovery by 

 Woods 1 of the interrelationship of these compounds with p-aminobenzoic 

 acid. Although not among the first analogues synthesized and tested, 

 sulfapyridine was the first of the ^-substituted sulfonamides found to 



ON— i 

 H 2 N-/ \-S0 2 -NH-C 



S — CH 

 sulfapyridine sulfathiazole 



be superior to sulfanilamide. Sulfapyridine was particularly outstanding 

 at the time for its curative effect in pneumonia, 89 and was apparently 

 first prepared by Ewins and Phillips 90 but was prepared by several 

 others. 91 One of the most potent of the sulfonamides, sulfathiazole, was 

 first reported by Fosbinder and Walter. 92 The synthesis of two more very 

 effective sulfonamides, sulfadiazine and sulfamethyldiazine (sulfamer- 

 azine), was first reported by Roblin, et aL 93 



HC CH 



3 2 N-f \-S0 2 -NH-C CH H 2 N-<f V* 



sulfadiazine sulfacetamide 



