Purines. LI. Synthesis and biological activity of hypoxanthine 7-N-oxide and related compounds. |
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Authors: | K Ogawa M Nishii F Nohara T Saito T Itaya T Fujii |
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Affiliation: | Research Laboratories, Ikeda Mohando Co., Ltd., Toyama, Japan. |
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Abstract: | A detailed account is given of the first chemical synthesis of hypoxanthine 7-N-oxide (5), which started from coupling of 6-chloro-5-nitro-4(3H)-pyrimidinone (7) with N-(4-methoxybenzyl)phenacylamine, generated in situ from the hydrochloride (8), and proceeded through cyclization of the resulting phenacylaminopyrimidinone (9) and removal of the 4-methoxybenzyl group. The results of catalytic hydrogenolysis, methylation followed by catalytic hydrogenolysis, and rearrangement under acidic conditions of 5 supported the correctness of the assigned structure. An ultraviolet spectroscopic approach suggested that the neutral species of 5 exists in H2O mainly as the N(7)-OH tautomer (21). In the in vitro bioassay of antileukemic activity against murine L5178Y cells, 5 was weakly cytotoxic, with IC50 of 100 micrograms/ml. It did not show any antimicrobial activity even at 1000 micrograms/ml. None of the 9-(4-methoxybenzyl) (11) and O-methyl (12, 13, and 14) derivatives was found to be antileukemic or antimicrobial. |
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