Aryl H-Phosphonates 17: (N-Aryl)phosphoramidates of Pyrimidine Nucleoside Analogues and Their Synthesis, Selected Properties, and Anti-HIV Activity
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- 作者：Joanna Romanowska ; Micha艂 Sobkowski ; Agnieszka Szyma艅ska-Michalak ; Krystian Ko艂odziej ; Aleksandra D膮browska ; Andrzej Lipniacki ; Andrzej Piasek ; Zofia M. Pietrusiewicz ; Marek Figlerowicz ; Andrzej Guranowski ; Jerzy Boryski ; Jacek Stawi艅ski ; Adam Kraszewski
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：October 13, 2011
- 年：2011
- 卷：54
- 期：19
- 页码：6482-6491
- 全文大小：944K
- 年卷期：v.54,no.19(October 13, 2011)
- ISSN：1520-4804
文摘
New synthetic protocol for the preparation of nucleoside 5鈥?(N-aryl)phosphoramidate monoesters 4 was developed. It consisted of a condensation of the corresponding nucleoside 5鈥?H-phosphonates with aromatic- or heteroaromatic amines promoted by diphenyl phosphorochloridate, followed by oxidation of the produced H-phosphonamidates with iodine/water. 5鈥?(N-Aryl)phosphoramidate monoesters derived from 3鈥?azido-3鈥?deoxythymidine (AZT) or 2鈥?3鈥?dideoxyuridine (ddU) nucleosides and various aromatic and heteroaromatic amines were evaluated as potential anti-HIV drugs. It was found that these compounds act most likely as pronucleotides and that some of them have therapeutic indices superior to those of the reference AZT.