Synthesis and Antiviral Activity of 5--2'-deoxyuridine

Article abstract of DOI:10.1021/jm00136a007

To study the influence of substitution of CN for C<*>CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-<(cyanomethylene)oxy>-2'-deoxyuridine (2) was prepared.When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated product 3-(cyanomethyl)-5-<(cyanomethylene)oxy>-2'-deoxyuridine (3) was the major product with a lesser amount of 3-(cyanomethyl)-5-hydroxy-2'-deoxyuridine (5) and only a trace amount of the desired product (2).In contrast, when 5-hydroxy-2'-deoxyuridine was alkylated in water in the presence of 1 equiv of KOH, compound 2 was the major product.In cultures of primary rabbit kindey (PRK) cells, compound 2 showed an anti-herpes virus activity that was comparable to that of 1 and ara-A.Compound 2 did not inhibit incorporation of 3H>dThd or <1',2'-³H>dUrd into DNA of PRK cells; however, its anti-herpes virus activity was completely prevented upon the addition of either dThd or dUrd.