Aryl H-Phosphonates 17: (N-Aryl)phosphoramidates of Pyrimidine Nucleoside Analogues and Their Synthesis, Selected Properties, and Anti-HIV Activity

作者：Romanowska Joanna; Sobkowski Michal; Szymanska Michalak Agnieszka; Kolodziej Krystian; Dabrowska Aleksandra; Lipniacki Andrzej; Piasek Andrzej; Pietrusiewicz Zofia M; Figlerowicz Marek; Guranowski Andrzej; Boryski Jerzy; Stawinski Jacek; Kraszewski Adam^*

来源：Journal of Medicinal Chemistry, 2011, 54(19): 6482-6491.

DOI：10.1021/jm2001103

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.

• 出版日期2011-10-13
• 单位河北医科大学