Purines. LI. Synthesis and biological activity of hypoxanthine 7-N-oxide and related compounds.
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.
Ogawa
K
K
Research Laboratories, Ikeda Mohando Co., Ltd., Toyama, Japan.
Nishii
M
M
Nohara
F
F
Saito
T
T
Itaya
T
T
Fujii
T
T
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006868:Hydrolysis; D007042:Hypoxanthines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008745:Methylation; D008826:Microbial Sensitivity Tests; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
D003497:Cyclic N-Oxides; D007042:Hypoxanthines; C075164:hypoxanthine 7-N-oxide