A series of acyclic nucleosides and related alpha-phosphonyl acyclic a
nalogues of dNTP with an amide bond have been prepared. Their antivira
l and substrate properties were investigated. New acyclic nucleoside a
nalogues with a rigid structural element, amide bond, have been synthe
sized in two stages. Alkylation of bis- trimethylsilylated thymine, cy
tosine and sodium salt of adenine by ethyl bromoacetate gave ethoxycar
bonylmethyl derivatives ($) under bar 1a-c. Reaction of ($) under bar
1a-c with aminoalcohols afforded acyclic nucleosides ($) under bar 2-(
$) under bar 4 in good yields (Scheme 1), These analogues were found t
o be inactive against HIV-1 (CEM-SS cells) and HSV -1, HSV-2, HCMV, VZ
V (HFF cells) at concentrations up to 100 mu g/ml and were nontoxic to
wards CEM and HFF cells. However, it was shown that triphosphate of ($
) under bar 2c is incorporated into the DNA chain by DNA polymerase fr
om HSV-1(1). The absence of antiviral activity and cytotoxicity is pro
bably due to the fact that ($) under bar 2-($) under bar 4 are not rec
ognized by cellular and viral kinases.