Synthesis and biological evaluation of phosphonated dihydroisoxazole nucleosides.

Phosphonated isoxazolinyl nucleosides have been prepared via 1,3-dipolar cycloaddition reaction of nitrile oxides with corresponding vinyl or allyl nucleobases for antiviral studies. The cytotoxicity, the anti-HSV activity and the RT-inhibitory activity of the obtained compounds were evaluated and compared with those of AZT and diethyl{(1'SR,4'RS)-1'-[[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)]-3'-methyl-2'-oxa-3'-azacyclopent-4'-yl]}methylphosphonate, a saturated phosphonated dihydroisoxazole nucleoside analogue.

Synthesis and biological evaluation of phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides.

The synthesis of carbocyclic 2'-oxa-3'-aza-nucleosides has been described, based on the 1,3-dipolar cycloaddition of a new phosphonated nitrone with vinyl acetate followed by coupling with silylated nucleobases. The obtained compounds have been evaluated for their ability to inhibit the reverse transcriptase of avian myeloblastosis retrovirus: no significant activity has been observed.

Synthesis of phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides: novel inhibitors of reverse transcriptase.

Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.