106 



AARON BENDICH 



thesis ;^^^<^ and results of preliminary application to human neoplastic dis- 

 gg^gg285e have stimulated further clinical trials with this drug. 



In 1901, Gabriel and Colman^^^ converted 4 , 5-diamino-6-methylpyrimi- 

 dine into 6-methyl-8-azapurine (or 7-methyl-l-i;-triazolo[c^]pyrimidine) 

 upon reaction with nitrous acid. The isosteric relationship of this compound 

 to 6-methylpurine2^ is obvious. With the expectation of preparing purine 

 antagonists, Roblin et al."^^ applied the above reaction to the appropriate 

 4,5-diaminopyrimidines and obtained the 8-aza analogues of adenine, of 

 guanine (XXXIII, or "guanazolo"), and of hypoxanthine. Those of adenine 

 and guanine exhibited an antibacterial activity (against E. coli and *S. 



OH 



I 



N 



NHo 



HONG 



H2N NH2 



2,4,5-Triamino-6- 

 hydroxypyrimidine 



H2N 



OH 



I 



N 



\ 



H 

 XXXIII 



8-Azaguanine 



NH 



NHo 



HN 



4-Amino-5-imidazole- 

 carboxamide 



XXXTV 



2-Azaadenine 



aureus), and this action was reversed by the respective parent purines. 

 Other 8-azapurines have been sjmthesized,^**'^^^ but 8-azaguanine has 

 provoked the most interest. It inhibits the growth of the guanine-requiring 

 protozoan T. geleii,'^^^ the mammary adenocarcinoma Eo 771 in C57 black 

 mice,2^^'2^2 and the development of several plant virus infections.^^' A 



286 S. Gabriel and J. Colman, Ber. 34, 1234 (1901). 



2" R. O. Roblin, Jr., J. O. Lampen, J. P. English, Q. P. Cole, and J. R. Vaughan, /. 



Am. Chem. Soc. 67, 290 (1945). 

 288 L. F. Cavalieri, A. Bendich, J. F. Tinker, and G. B. Brown, /. Am. Chem. Soc. 70, 



3875 (1948). 

 28» P. Bitterli and H. Erlenmejer, Helv. Chim. Acta, 34, 835 (1951). 



290 G. W. Kidder and V. C. Dewey, /. Biol. Chem. 179, 181 (1949). 



291 G. W. Kidder, V. C. Dewey, R. E. Parks, Jr., and G. L. Woodside, Science 109, 511 

 (1949). 



