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 5'-monophosphates, and their efficiency correlated well with the pK(a) values of the aryloxy groups present.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-HIV Agents / chemical synthesis*
-
Anti-HIV Agents / chemistry
-
Anti-HIV Agents / pharmacology
-
Cell Line
-
Cells, Cultured
-
HIV / physiology
-
Humans
-
Hydroxy Acids / chemical synthesis
-
Hydroxy Acids / chemistry
-
Hydroxy Acids / pharmacology
-
Microbial Sensitivity Tests
-
Molecular Structure
-
Nucleosides / chemical synthesis*
-
Nucleosides / chemistry
-
Nucleosides / pharmacology
-
Nucleotides / chemical synthesis*
-
Nucleotides / chemistry
-
Nucleotides / pharmacology
-
Organophosphonates / chemical synthesis*
-
Organophosphonates / chemistry
-
Organophosphonates / pharmacology
-
Virus Replication / drug effects
Substances
-
Anti-HIV Agents
-
Hydroxy Acids
-
Nucleosides
-
Nucleotides
-
Organophosphonates