154 Essays in Biochemistry 



replaced by the 5-tetrazolyl group. This thought suggests that a 

 series of antimetabolites in which the 5-tetrazolyl group replaces the 

 carboxyl group as an acidic function is conceivable. For instance, 

 amino acid analogs in which the tetrazolyl group replaces the carboxyl 

 group might serve as effective amino acid antimetabolites. Such an- 

 tagonists could serve a useful purpose in the study of the effects of 

 interference with the utilization of various amino acids normally occur- 

 ring in plant and animal proteins. It is also conceivable that malfunc- 

 tions in the utilization of specific amino acids produced by such anti- 

 metabolites could lead to a better understanding of protein and amino 

 acid metabolism. Furthermore, such antimetabolites could be useful 

 in controlling pathological states associated with hyperactivity of 

 amino acid and protein metabolism. At this time only one such com- 

 pound is known, the 5-/?-aminoethyltetrazole which was prepared as 

 a histamine analog by Ainsworth. 14 It failed to exhibit either hista- 

 minelike properties or histamine antagonism, observations that are not 

 surprising since the compound should more properly be considered as 

 a ^-alanine analog, an analogy which was not recognized at the time. 



Beyond this only simple aliphatic and aromatic carboxylic acid 

 analogs have been studied. Although the 5-alkyltetrazoles have shown 

 some interesting pharmacological properties as rather potent anticon- 

 vulsant agents as measured by their antagonism towards Metrazole, 

 no compounds have been prepared with long-chain alkyl groups which 

 would make them comparable to fatty acids such as palmitic and 

 stearic. Such long-chain compounds could be of interest in their rela- 

 tionship to fatty acid metabolism in the living organism. Although 

 the biological implications associated with the 5-substituted tetrazoles 

 are purely speculative at this time, the preparation and study of such 

 compounds in the future could lead to interesting organic and bio- 

 chemical results. 



This discussion is based upon experimental work done by Drs. 

 Joseph S. Mihina, William L. Garbrecht, and James A. Garrison, and 

 Mr. Kenneth R. Wilson. The literature concerning tetrazoles has been 

 reviewed by Benson 1 to whom reference should be made for the earlier 

 work. 



References 



1. F. R. Benson, Chem. Revs., 41, 1 (1947). 



2. J. S. Mihina and R. M. Herbst, J. Org. Chem., 15, 1082 (1950). 



3. W. L. Garbrecht and R. M. Herbst, J. Org. Chem.., IS, 1003 (1953). 



4. W. L. Garbrecht and R. M. Herbst, J. Org. Chem., IS, 1014 (1953). 



