STEREOCHEMICAL ASPECTS OF THE ANTI-HCMV ACTIVITY OF CYTIDINE NUCLEOSIDE ANALOGS

The remarkable selectivity of the beta-L enantiomers of 2',3'-dideoxycytidine analogues against the viral polymerases of HIV and HBV has stimulated our interest in targeting beta-L enantiomers of anti-HCMV cytidine analogues. Indeed, Ara-C, FIAC and DMDC are cytidine analogues with beta-D configuration that show significant potency as anti-HCMV agents but lack selectivity, beta-L enantiomers have therefore been synthesized and evaluated together with four other nucleoside analogues, and the beta-L enantiomers were found not to be inhibitory to HCMV replication. However, the three alpha-L isomers, alpha-L-Ara-C, alpha-L-Xylo-C and alpha-L-FMAU, emerged with activity against HCMV and have provided new approaches for the treatment of viral diseases with nucleoside analogues possessing the unusual L-configuration,