THE FOLIC ACID GROUP 581 



The analogue with a combination of two methyl groups at the 9- and 

 N 10 -positions (9,N 10 -dimethylfolic acid) is considerably more effective 

 than 9-methylfolic acid in inhibiting the growth of Streptococcus faecalis 

 R, but is less effective than N 10 -methylfolic acid. 



Substituted Pteroic Acids and Related Compounds. A larger group, 

 such as phenacyl, in the N 10 -position appears to be detrimental to the 

 inhibitory activity of an analogue. This is indicated more clearly in the 

 pteroic acid series of N 10 -derivatives, which become progressively less 

 effective as antagonists of folic acid for Streptococcus faecalis R as the 

 size of the substituent group increases from the N 10 -methyl (Table 19). 



OH 



C N CH 3 



N C C— CH 2 — N— (' \— COOH 



i ii i x^/ 



H 2 N— C C CH 



X / \ / 



N N 



N i0 -methylpteroic acid 



The pteroic acid analogues are as a general rule less effective than the 

 corresponding folic acid analogues. Although the data in Table 19 indi- 

 cate that z-methylpteroic acid approaches the activity of z-methylfolic 

 acid, it is only 10 to 20 per cent as effective as x-methylfolic acid in pre- 

 venting the utilization of folic acid by Streptococcus faecalis R when 

 the two analogues are tested under identical conditions. 108, 126 The chloro- 

 methylpteroic acid prepared from 4-amino-2-chlorobenzoic acid, cc,/?- 

 dibromobutyraldehyde and 2,4,5-triamino-6-hydroxypyrimidine is ap- 

 proximately as inhibitory as .r-methylfolic acid. It is interesting that 

 4-amino-2-chlorobenzoic acid can replace p-aminobenzoic acid in this 

 folic acid analogue without appreciably altering its inhibitory action, and 

 can also inhibit the utilization of p-aminobenzoic acid by Escherichia 

 coli (p. 524) . 



OH 



. I 



C N 



N C C— CO— NH— V \— CO— NH— CH— CH 2 — CH 2 — COOH 



I II I \_/ I 



H 2 N— C C C— OH COOH 



7-hydroxy-9-oxofolic acid [N-(N-(2-amino-4,7-dihydroxypteridine-6-car- 

 boxyhjl)-p-aminobenzoyl)~'L-glutamic acid] 



