Aryl nucleoside H-phosphonates. Part 16: synthesis and anti-HIV-1 activity of di-aryl nucleoside phosphotriesters

ROMANOWSKA J;SZYMANSKA MICHALAK A;BORYSKI J;STAWINSKI J;KRASZEWSKI A;LODDO, ROBERTA;SANNA, GIUSEPPINA;COLLU G;SECCI, BARBARA;LA COLLA P.

2009-01-01

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Abstract

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 50-monophosphates, and their efficiency correlated well with the pKa values of the aryloxy groups present.