p-AMINOBENZOIC ACID 



495 



Sulfacetamide (albucid) , 94 because of low toxicity, is useful in urinary- 

 infections. Sulfaguanidine, 95, ° 6 succinylsulfathiazole, 97, 9S and phthalyl- 

 sulfathiazole ° 7, 9S have been synthesized and, being sparingly absorbed 

 from the bowel, are useful in treatment of intestinal infections. 



Table 5. Sulfonamides, Sulfones, Sulfoxides and Related Inhibitory Analogues of 

 p-Aminobenzoic Acid 



Supplemen- 

 Inhibition Efficiency tary 



Index Ratio References 



Compound 



Sulfadiazine 



Sulfacetamide 



Sulfaguanidine 



Sulfanilic acid 



bis(4-Amino- 

 phenyl)sulfone 



Organism 



Escherichia coli 

 Staphylococcus aureus 

 Mycobacterium tuberculosis 

 Pasteurella pestis 

 Proteus vulgaris 

 Escherichia coli 

 Staphylococcus aureus 

 Streptococcus hemolyticus B 

 Neisseria gonorrhoeae 

 Escherichia coli 

 Staphylococcus aureus 

 Streptococcus hemolyticus B 

 Saccharomyces cerevisiae 139 

 Streptococcus hemolyticus 

 Escherichia coli 



Streptobacterium plantarum 10 S 

 Staphylococcus aureiis 



Escherichia coli 

 Mycobacterium tuberculosis 

 Streptobacterium plantarum 10 S 

 Streptococcus hemolyticus B 



Other sulfonamides, sulfones, sulfoxides and related compounds the toxicity of which is prevented by 

 p-aminobenzoic acid include: N l -arylsulfanilamides: N'-phenyl-, 130 N'-o-tolyl-, 130 N'-o-chlorophenyl-, 130 

 N^o-hydroxyphenyl-, 130 N^p-hydroxyphenyl-, 130 N'-p-aminophenyl-, 130 N'-p-nitrophenyl-, 127 and N l -m- 

 carboxyphenylsulfanilamides, 130 and N'.N'-dimethyl-l-sulfanilamidobenzenesulfonamide. 127, 129 ' 13 ° N 1 - 

 Heterocyclicsulfanilamides: 2-sulfanilamido derivatives of pyrimidine, 151 4-methylpyrimidine, 130 5-chloro- 

 pyrimidine, d 156 6-bromopyrimidine, <i 156 4-amino-5-bromopyrimidine, 156 5-bromo-4-methylpyrimidine, 156 

 5-bromo-4,6-dimethylpyrimidine, 156 5-(2,3-dibromopropyl)-4, 6-dimethylpyrimidine, 156 4-methylthia- 

 zole, 127 ' 130 4-phenyl-5-methylthiazole, 127, 13 ° 5-bromothiazole, 159 5-chlorothiazole, 156 5-bromo-4-methyl- 

 thiazole, 156 5-chloro-4-methylthiazole, 156 5-pyridinesulfonamide, 127 ' l3 ° 4-methyldiazine, 110 4,6-dimethyl- 

 diazine, 110 5-chloropyridine, 156 thiazoline, 127, 130 5-methylthiadiazole, 121, m 5-ethylthiadiazole, 121 ' 131 

 5-7i-propylthiadiazole, 121 5-isopropylthiadiazole, 121 and 5-isobutylthiadiazole 121 and 2-(2-chlorosulfanila- 

 mido)pyrimidine 156 and 3,4-dimethyl-5-sulfanilamidoiso-oxazole. 157 N l -Acylsulfanilamides and miscellaneous 

 sulfonamides: N 4 -sulfoxymethylsulfanilamide (sodium salt), 130 N'-3,4-dimethylbenzoylsulfanilamide, 158 

 sulfanilamidoacetic acid, 130 p-hydroxylaminobenzenesulfonamide. 101 Sulfones and sulfoxides: 2-amino- 

 phenyl 4-aminophenyl sulfone, 154 bis(2-aminophenyl)sulfone, 164 bis(3-aminophenyl) sulfone, 154 4-ace- 

 tylaminophenyl 4-nitrophenyl sulfone, 154 4-aminophenyl 4-hydroxyphenyl sulfone, 49 4-aminophenyl 

 4-benzylidineaminophenyl sulfone, 154 4-aminophenyl 5-amino-2-pyridyl sulfone,' 59 promin, 155 bis(4-amino- 

 phenyi) sulfoxide, 149, I54 bis(4-acetamidophenyl)sulfoxide, 154 4-aminophenyl phenyl sulfoxide, 154 4-amino- 

 phenyl 4-nitrophenyl sulfoxide, 49 ' 154 4-acetamidophenyl 4-nitrophenyl sulfone 49, 154 4-aminophenyl 4-chlo- 

 rophenyl sulfone, 154 4-aminophenyl 4-iodophenyl sulfone, 154 4-iodophenyl 4-nitrophenyl sulfone. 154 

 Miscellaneous Analogues: p-aminophenyldimethylsulfonium /3-naphthalenesulfonate, 160 bis(4-aminophenyl) 

 disulfide, 109 bis(4-aminophenyl)diselenide. d109 



° Ratio of the activity of the sulfonamide to that of sulfanilamide. 100 



6 For half-maximum growth. 



Molecular equivalents of sulfonamide neutralized by one molecular equivalent of p-aminobenzoic acid. 



d Toxicity of these compounds only partially reversed by p-aminobenzoic acid. 



The remarkable chemotherapeutic activity of this group of compounds 

 has stimulated the preparation of thousands of compounds somewhat 

 related in structure to sulfanilamide. An excellent monograph by 

 Northey " on sulfonamides and related compounds includes comprehen- 



