8-Azaguanine nucleosides

The acyclic 8-azaguanine nucleosides having (2-hydroxyethoxy)methyl-or [2-hydroxy-l-(hydroxymethyl)ethoxy]methyl moieties at N-9 were screened against herpes simplex virus type 1 (HSV1) (85JMC982 86-EUP201289). 

Azaguanosine was obtained by the action of phosphomonoesterase on the nucleotide. Oxidation of the nucleoside with sodium metaperiodate, followed by incubation at pH 10 at 37°, released 8-azaguanine. 

Both ribose-l-P and deoxyribose-l-P serve as sugar donors in the synthetic reaction. In addition to the naturally occurring purines, certain purine analogues can also serve as substrates or inhibitors of purine nucleoside phosphoiylase. Of these, 8-azaguanine, 6-mercaptopurine, 6-thio-guanine, and allopurinol bind most tightly to the human erythrocyte enzyme 17). 

It is well established that aza analogs of purines, pyrimidines and their nucleosides possess significant but varying potency as antineoplastic agents [1-7]. Thus, for example, 6-azacytidine is an inhibitor for orotidylic acid decarboxylase [3] and 6-azauracil inhibits the development of animal tumors [4] and human acute leukemia [5] similarly, 8-azaguanine is a highly effective anti-neoplastic agent [6] and also inhibits animal tumors [7]. 

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