THIAZOLO[4,5-D]PYRIMIDINES - PART II - SYNTHESIS AND ANTI-HUMAN CYTOMEGALOVIRUS ACTIVITY IN-VITRO OF CERTAIN ACYCLONUCLEOSIDES AND ACYCLONUCLEOTIDES DERIVED FROM THE GUANINE ANALOG 5-AMINO-THIAZOLO[4,5-D]PYRIMIDINE-2,7(3H,6H)-DIONE

The synthesis and in vitro antiviral activity of certain hydroxyalkoxy methyl, hydroxyalkyl, hydroxyalkenyl and phosphonoalkenyl derivatives of the guanine congener 5-aminothiazolo-[4,5-d]pyrimidine-2,7(3H,6H)-d ione are reported. The compounds of this study were selected for their structural similarity to acyclonucleosides with known anti-herpesviru s activity. en-1-yl]thiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione was the only member of the series to display significant in vitro activity ag ainst human cytomegalovirus (HCMV); however, this compound did not inh ibit other herpesviruses, human immunodeficiency virus type 1 or murin e cytomegalovirus. It was found to have a cytotoxicity profile similar to that of ganciclovir (DHPG). The antiviral effect was found to be s ensitive to the initial viral input and the time of addition during th e virus replication cycle. Significantly, the compound was found to ha ve equal anti-HCMV activity, against standard virus strains, to DHPC, but also showed potent activity against DHPG-resistant virus strains, except for a strain mutated in the UL97 (phosphotransferase) gene.