p-AMINOBENZOIC ACID 527 



active than sulfanilamide for several organisms (Table 9). The latter 

 compound is approximately ten times as active as sulfanilamide for 



HC CH HC CH 



N0 2 — C C— CO— NH 2 CH 3 — CO— NH— C C— CO— CH 3 



5-nitrothiophene~2-carboxamide meihyl-2-(5-acetamidothienyl) ketone 



Escherichia coli. While the heterocyclic amide is approximately ten times 

 as active as the free acid for Escherichia coli, the acid is approximately 

 twice as effective as the amide against both Streptococcus hemolyticus 

 Group A and Diplococcus pneumoniae Type III. The corresponding amino 

 compound, 5-aminothiophene-2-carboxamide, is inactive as an inhibitor 

 for these organisms. 16 Methyl 2-(5-acetamiclothienyl) ketone is more 

 active than sulfanilamide in inhibiting growth of Escherichia coli, but is 

 somewhat less effective against Streptococcus hemolyticus and Diplococ- 

 cus pneumoniae. A similar situation exists for 6-aminonicotinic acid, 

 which is several times as active as sulfanilamide against Escherichia 

 coli and is essentially as active against Streptococcus hemolyticus; but 

 the analogue does not inhibit the growth of Diplococcus pneumoniae 

 Type III. It is interesting that this analogue is reported to be an antag- 

 onist of nicotinic acid rather than of p-aminobenzoic acid in Staphylococ- 



-COOH 

 NH 2 



6-aminonicotinic acid 



cus aureus. 420 The pyrimidine derivative corresponding to this pyridine 

 analogue, 2-amino-5-pyrimidinecarboxylic acid, is reported to have slight 

 activity in preventing the toxicity of sulfonamides (p. 484) . 



Ketone Analogues. As indicated in Table 9, p-aminophenyl ketones 

 are very effective inhibitory analogues of p-aminobenzoic acid. p,p'- 

 Diaminobenzil is several times as active as sulfanilamide in inhibiting 

 the growth of either Streptobacterium plantarum or Staphylococcus 

 pyogenes. This combination of two carbonyl groups results in a more 

 effective inhibitor than a single carbonyl. Thus, the diketone is approx- 

 imately 20 to 60 times as effective as p,p'-diaminobenzophenone. Slight 

 chemotherapeutic activity was observed with p,p'-diaminobenzophenone 



H 2 N-/ \_ CO— CO— / \-NH 2 H 2 N-/ \_CO— / VnH, 



p ,p '-diaminobenzil p,p'-diaminobenzophenone 



