Aryl nucleoside H-phosphonates. Part 16: synthesis and anti-HIV-1 activity of di-aryl nucleoside phosphotriesters.
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.
Romanowska
Joanna
J
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.
Szymańska-Michalak
Agnieszka
A
Boryski
Jerzy
J
Stawiński
Jacek
J
Kraszewski
Adam
A
Loddo
Roberta
R
Sanna
Giuseppina
G
Collu
Gabriella
G
Secci
Barbara
B
La Colla
Paolo
P
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D006678:HIV / Q000502:physiology; D006801:Humans; D006880:Hydroxy Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D006880:Hydroxy Acids; D009705:Nucleosides; D009711:Nucleotides; D063065:Organophosphonates