ANALOGUES 



short time, the organisms beginning to grow again after forty-eight 

 hours. It would appear, therefore, that some organisms are able to 

 convert these two substances readily into ^-aminobenzoic acid, whereas 

 others can do so only with difficulty. 



Johnson et al. prepared thirty-five other compounds related to 

 ^-aminobenzoic acid and tested their effect on the growth of E. coli, 

 S. haemolyticus and D. pneumoniae. The results of their work can be 

 summarised as follows : Substitution of ^-aminobenzoic acid in the 2- 

 or 3-position with, for example, a methyl or methoxy group or a halogen 

 atom yielded bacteriostatic compounds, and the introduction of a 

 second group destroyed the activity. Replacement of the amino 

 group by any group other than the nitro group gave an inactive 

 substance, whilst replacement of the carboxyl group had a variable 

 result. Thus, ^-aminoacetophenone and 3-methyl-4-aminobenzamide 

 had bacteriostatic properties, whilst other compounds of this type 

 showed growth-promoting activity and yet others were completely 

 inactive. 4-Amino-4'-carboxydiphenylamine inhibited the growth of 

 Strep, haemolyticus, Staph, aureus and E. coli to the same extent as 

 sulphanilamide. '^° 



2-Chloro-4-aminobenzoic acid exhibited curious properties and was 

 a growth factor for S. haemolyticus and D. pneumoniae but a growth 

 inhibitor for E. coli at high concentrations and had anti-sulphanilamide 

 properties at lower concentrations. 



The only naphthalene compound tested, 4-amino-i-naphthoic acid, 

 was bactericidal at high, but inactive at low, concentrations. Two 

 thiophene compounds, 5-nitrothiophene-2-carboxamide and 5-nitro- 

 thiophene-2-carboxylic acid were highly inhibitory towards S. haemo- 

 lyticus, but the former was ten times as active as the latter against 

 E. coli. The only thiazole compound tested, 2-aminothiazole-5- 

 carboxylic acid, was inactive and both 5-nitro-2-furoic acid and 

 5-acetylamino-furoic acid were inactive. 6-Aminopyridine-3-carboxylic 

 acid, however, was as active as sulphanilamide against 5. haemolyticus 

 and eight times as active against E. coli, being about as active as 

 sulphapyridine against both organisms. 



_/)-Aminobenzoic acid reversed the activity of all the compounds 

 that had bacteriostatic properties. 



2-AminopyTimidine-5-carboxylic acid had no antibacterial action 

 on Strep, pyogenes in vitro, but had a slight antagonistic effect towards 

 sulphanilamide, although inferior in this respect to ^-aminobenzoic 

 acid.® Of a series of derivatives of ^-aminobenzoic acid substituted 

 in the nucleus, the most potent antibacterial substances were 3-hydroxy- 

 and 3-chloro-4-aminobenzoic acid and 3 : 4-diaminobenzoic acid.^* ^^ 

 The first of these had one-third to one-ninth the activity of sulphanil- 

 amide and had a definite but feeble therapeutic effect in mice infected 

 36 561 



