THIAMINE 699 



formation of a secondary amine by combination of the amino group of 

 the "activator" with the 5-methylenc group of the pyrimidine component 

 of the thiamine. They succeeded in isolating N-(2-methyl-4-amino-5- 

 pyrimidylmethyl)-m-nitroanilinc from the reaction mixture produced 

 when thiamine was enzymatically destroyed in the presence of ?>i-nitro- 

 aniline. 



Sealock and Goodland 93 found that the cleavage of thiamine by the 

 Chastek paralysis enzyme is inhibited by a number of thiazole deriva- 

 tives. 3-o-Aminobenzyl-4-methylthiazolium chloride at a concentration 



ci- 



aCH 2 — N+ C— CH 3 

 NH 2 H i! L 



\ / 



S 



3-o-aminobenzyl-4-methyUhiazolium chloride 



of 5 X 10~ 4 mole/liter was found to produce 100 per cent inhibition of the 

 enzymatic destruction of thiamine at the same molar concentration, and 

 the extent of the inhibition proved to be dependent upon the inhibitor- 

 thiamine ratio. A like concentration of 3-/?-aminoethyl-4-methylthia- 

 zolium chloride caused 56 per cent inhibition of the destruction of the 

 vitamin. The other compounds tested (3-o-nitrobenzyl-, 3-/3-phthalimido- 

 ethyl-, 3-ethyl-, 3-phenyl-, 3-ethyl-2-methyl-, and 3-methyl-5-/3- 

 hydroxyethyl-4-methylthiazolium chlorides as well as several 6-amino- 

 pyrimidine compounds) were either only slightly effective or completely 

 without activity as inhibitors. The importance for inhibitory activity of 

 the amino group in the position analogous to that of the 4'-amino group 

 of thiamine is indicated by the high activity of the o-aminobenzyl deriva- 

 tive and the low activity of the corresponding compounds which do not 

 possess this group. Further evidence for the importance of the position 

 of the amino group in the benzyl portion of the thiazole derivative was 

 obtained by Sealock and Livermore, 94 who showed that whereas the 

 o-aminobenzyl derivative was highly inhibitory, the corresponding 

 p-aminobenzyl analogue was almost without inhibitory action and the 

 m-aminobenzyl compound was markedly stimulatory. It was also demon- 

 strated that the 4-methyl group is not an essential feature of the inhibitor 

 molecule, for the corresponding 2-methyl derivative had equal or slightly 

 greater inhibitory action. However, placing a methyl group in both the 

 2 and 4 positions of the thiazole ring resulted in a compound with less 

 than 50 per cent of the inhibitory activity of the corresponding analogues 

 in which only one of those positions was substituted. 



