Virus-specific enzymes essential for viral nucleic acid replication or related functions are targets for inhibition by substrate or product nucleotide analogues in which one or more P-O bonds are replaced by a P-C bond. The simplest examples of these are PFA (phosphonoformic acid ) and PAA (phosphonoacetic acid), representing analogues of 'pyrophosphate' moieties in nucleotides. The synthesis of a series of α-halogenated and α-οxο PAA and MDP (methanediphosphonate) derivatives is described and structure/activity relationships in their inhibition of several human (α,β,γ) and viral (HSV, EBV, HIV) DNA polymerases are present ed. Inhibition of HIV RNA-directed DNA polymerase (reverse transcriptase) by PFA, α-oxophosphonoacetate and α-oxomethanediphosphonate is shown to be pH-and template-dependent. Combination of phosphonoacetate derivatives and anti-viral nucleo sides into 'hybrid' nucleotide analogues is brief ly discussed.Viruses, infecting and reproducing within host cells, have long been an elusive target for chemotherapy. However, recent advances in 3
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Organo-phosphorus compounds S 0080 Synthesis of α-Fluorinated Phosphonoacetate Derivatives Using Electrophilic Fluorine Reagents: Perchloryl Fluoride versus 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane Bis(tetrafluoroborate) (Selectfluor®). -Selectfluor® is an efficient reagent for the preparation of α-fluorinated phosphonoacetates (II), (III), and (XII). High-yielding procedures are developed for the synthesis of the corresponding diacids (VI) and (IX), and triacids (VII) and (X). -(MARMA, M. S.; KHAWLI, L. A.; HARUTUNIAN, V.; KASHEMIROV, B. A.; MCKENNA*, C. E.; J. Fluorine
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