Journal of medicinal and pharmaceutical chemistry 2011-10-13

Aryl H-phosphonates 17: (N-aryl)phosphoramidates of pyrimidine nucleoside analogues and their synthesis, selected properties, and anti-HIV activity.

Joanna Romanowska, Michał Sobkowski, Agnieszka Szymańska-Michalak, Krystian Kołodziej, Aleksandra Dąbrowska, Andrzej Lipniacki, Andrzej Piasek, Zofia M Pietrusiewicz, Marek Figlerowicz, Andrzej Guranowski, Jerzy Boryski, Jacek Stawiński, Adam Kraszewski

Index: J. Med. Chem. 54 , 6482-91, (2011)

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Abstract

New synthetic protocol for the preparation of nucleoside 5'-(N-aryl)phosphoramidate monoesters 4 was developed. It consisted of a condensation of the corresponding nucleoside 5'-H-phosphonates with aromatic- or heteroaromatic amines promoted by diphenyl phosphorochloridate, followed by oxidation of the produced H-phosphonamidates with iodine/water. 5'-(N-Aryl)phosphoramidate monoesters derived from 3'-azido-3'-deoxythymidine (AZT) or 2',3'-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.