Romanowska Joanna, Szymańska-Michalak Agnieszka, Boryski Jerzy, Stawiński Jacek, Kraszewski Adam, Loddo Roberta, Sanna Giuseppina, Collu Gabriella, Secci Barbara, La Colla Paolo
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.
Bioorg Med Chem. 2009 May 1;17(9):3489-98. doi: 10.1016/j.bmc.2009.02.033. Epub 2009 Feb 23.
Di-aryl nucleoside phosphotriesters have been explored as a new type of pronucleotides for the purpose of anti-HIV-1 therapy and efficient synthetic protocols, based on H-phosphonate chemistry, have been developed for the preparation of this class of compounds. It was found that anti-HIV-1 activity of the phosphotriesters bearing an antiviral nucleoside moiety (AZT, ddA) and also ddU was due, at least partially, to intracellular conversion into the corresponding nucleoside 5'-monophosphates, and their efficiency correlated well with the pK(a) values of the aryloxy groups present.
二芳基核苷磷酸三酯已被作为一种新型前体药物用于抗HIV-1治疗的研究，并且基于H-膦酸酯化学已开发出用于制备这类化合物的高效合成方案。研究发现，带有抗病毒核苷部分（齐多夫定、双脱氧腺苷）以及双脱氧尿苷的磷酸三酯的抗HIV-1活性至少部分归因于其在细胞内转化为相应的核苷5'-单磷酸，并且它们的效率与所存在的芳氧基的pK(a)值密切相关。
