NICOTINIC ACID (nIACIN) 



i8. ANALOGUES OF NICOTINIC ACID 

 Activity in Canine Blacktongue 



The first report of the effects in pellagra and blacktongue of com- 

 pounds other than nicotinic acid was that of Woolley et al.} who found 

 that only j8-picoline and the ethyl ester, amide and (to a smaller 

 extent) N-methylamide of nicotinic acid, cured blacktongue in dogs ; 

 picolinic acid {pyridine-2-carboxylic acid), quinolinic acid (pyridine- 

 2 : 3-dicarboxylic acid), isonicotinic acid (pyridine-4-carboxylic acid), 

 nipecotic acid (hexahydronicotinic acid), nicotinic acid diethylamide, 

 6-methylnicotinic acid, trigonelline, pyridine and N^-methylnicotin- 

 amide were inactive. SubbaRow et al} reported that ^-aminopyridine 

 was as effective as nicotinic acid in curing blacktongue in dogs, whilst 

 Najjar et al,,^ in contradiction to the findings of Woolley et al.,^ reported 

 that nicotinic acid diethylamide and N^-methylnicotinamide were 

 active and that the latter prevented fatty liver formation in rats, so 

 that its methyl group was apparently biologically active also.* Ac- 

 cording to Smith et al.^ the diethylamide had i/i5th the activity of 

 nicotinic acid, whilst L. J. Teply and C. A. Elvehjem ^ also found it 

 to be active. 



A difference of opinion also exists in respect of the activity of 

 nicotinuric acid which, according to Najjar et al.,^ was effective and, 

 according to J. W. Huff and W. A. Perlzweig ' and W. J. Dann and 

 P. Handler,^ ineffective. Again, Teply et al.^ found that N^-methyl- 

 nicotinamide was inactive, thus confirming Woolley's observation and 

 contradicting the results obtained by Najjar et al.^ 



On the other hand, there appears to be general agreement that 

 quinolinic acid,^' ^* ^^' ^^ and trigonelline i' ^ are inactive, and that 

 pyrazine-monocarboxylic acid (I) and pyrazine-dicarboxylic acid (II), 

 which obviously bear a close structural relationship to nicotinic acid : 



^ \cOOH / \cOOH 



(I) (II) 



and therefore might be expected to show some activity, are of no 

 value in the treatment of blacktongue.^^* ^^ Thiazole-5-carboxylic 

 acid,^^ pyrimidine-4-carboxylic acid,^^ 3-aminopyridine ^^ and 2-amino- 

 nicotinic acid ^^ were also inactive. 



Badgett et al.^^ prepared a series of fourteen esters of nicotinic 

 acid and fourteen substituted amides of such a type that when 

 added to cereals, no appreciable loss of the vitamin would occur on 

 rinsing the cereal with water. The ethyl and lauryl esters and the 



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