Purines. LXX. An Extension of the "Phenacylamine Route" to the Syntheses to the 7-N-Oxides of 6-Mercaptopurine and 6-Methylthiopurine, and Antileukemic Activity of Some Purine N-Oxides

• 藤井 澄三

  Faculty of Pharmaceutical Sciences, Kanazawa University

• 小川 和男

  Faculty of Pharmaceutical Sciences, Kanazawa University

• 板谷 泰助

  Faculty of Pharmaceutical Sciences, Kanazawa University

• 伊達 忠正

  Organic Chemistry Research Laboratory, Tanabe Seiyaku, Co., Ltd.

• 稲垣 甚一郎

  Research Laboratories, Ikeda Mohando Co., Ltd.

• 野原 富士夫

  Research Laboratories, Ikeda Mohando Co., Ltd.

抄録

A full account is given of the first syntheses of 6-mercaptopurine 7-N-oxide (4) and 6-methylthiopurine 7-N-oxide (5). The synthesis of 4 followed a "phenacylamine route", which started from condensation of 4,6-dichloro-5-nitropyrimidine (15) with N-(4-methoxybenzyl)phenacylamine to form the phenacylaminopyrimidine derivative (11) and proceeded through conversion into the mercapto derivative, intramolecular cyclization between the NO_2 nitrogen atom and the phenacyl carbanion to give 6-mercapto-9-(4-methoxybenzyl)purine 7-N-oxide (12), and removal of the 4-methoxybenzyl group. S-Methylation of 12 and removal of the 4-methoxybenzyl group afforded 5. The location of the oxygen function in 4,5,and 12 was confirmed by X-ray crystallographic analysis of 5・H_2O, which was shown to exist in the N(7)-OH form (19). A UV spectroscopic approach suggested that the neutral species of 4 exists in H_O as the N(7)-OH tautomer (21), whereas that of 5 exists as an equilibrated mixture of the N(7)-oxide (5) and the N(7)-OH (19) tautomers. In the in vitro bioassay of antileukemic activity against murine L5178Y cells, the N-oxides 4 and 12 were found to be weakly cytotoxic.

収録刊行物

• Chemical & pharmaceutical bulletin

  Chemical & pharmaceutical bulletin 43 (3), 408-413, 1995-03-15

  公益社団法人日本薬学会

キーワード

• 6-mercaptopurine 7-N-oxide
• 6-methylthiopurine 7-N-oxide
• synthesis
• X-ray analysis
• cyclization nitro-phenacylamino
• antileukemic activity

詳細情報

• CRID: 1572261552255268864
• NII論文ID: 110003631487
• NII書誌ID: AA00602100
• ISSN: 00092363
• 本文言語コード: en
• データソース種別:
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