โ Scribed by Foye, William O. ;Jeffrey, J. George
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A number of o-hydroxyazopyrimidines has been prepared for anticancer testing. These compounds were obtained by direct coupling into the pyrimidine ring, COU- pling of a diazotized aminopyrimidine into a phenol ring, or coupling of a diazotized aminophenol with acetoacetic ester followed by ring closure with urea or thiourea. Both spectral and chemical evidence suggest that these compounds exist more as quinone hydrazones than as azo compounds. T h e o-hydroxyazopyrimidines chelated heavy metal ions bur did not show appreciable activity against Sarcoma 180. ECENT ATTEMPTS t o find possible antagonists R t o the formation of nucleic acids in the animal have led to the synthesis of numerous pyrimidine derivatives. Anticancer tests on these compounds have revealed growth-retarding effects on tumors from a number of them, notably 6-mercaptopurine and 8-azaguanine (1). 2-Thiouracil has also shown ability to decrease incidence of liver cancer, while uracil itself overcomes this inhibition ( 2 ) . Since a number of azo compounds have shown both cancer-producing and cancer-inhibiting activities (3), a series of azo derivatives of some pyrimidines, mainly uracil and substituted uracils, has been synthesized and tested for cancer chemotherapeutic action. In addition, these azo compounds were prepared having hydroxy groups ortho to the azo linkage, thereby making them theoretically capable of chelating heavy metals. This should provide an opportunity for testing the effect of a metal-chelating agent on cancer growth; it has been suggested b y Boyland and Watson (4), for instance, that the carcinogenic effects of various o-aminophenols may he due to metal chelation in ViZIO.
Methods of Synthesis.--The preparation of the azopyrimidines was first attempted by the direct coupling of a diazonium salt with uracil or its relatives. The compound 5-phenylazouracil had been prepared previously by Bogert and Davidson (5) from isodialuric acid and phenylhydrazine, but no melting point was listed; direct coupling of benzenediazonium chloride with uracil gave a product
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