Analogues of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbutyl)guanine. Part 4. Substitution on the 2-amino group

Abstract

Syntheses of 2-N-substituted derivatives of antiviral acyclonucleosides are described. Analogues of 9-(4-hydroxy-3-hydroxymethylbutyl)guanine (1b) with alkyl (6), aryl (7) and (8), amino (9), methoxy (10), and hydroxy (11) substituents on the 2-amino group were prepared by reaction of the appropriate amine with the 2-chloropurine (5). The 2-N-hydroxy derivatives (23a, b) of the 9-alkoxyguanines (1c, d) were synthesized by cyclisation of imidazole intermediates (20a, b) to the 2-thiopurines (21a, b) followed by oxidation and hydroxylamine displacement at the 2-position. The 2-N-hydroxyguanines (11) and (23a) showed potent antiherpes virus activity in cell culture tests.