Relationship between Conformation and Antiviral Activity-II. 5-Methoxymethyl-2′-deoxycytidine and 5-methoxymethyl-N⁴-methyl-2′-deoxycytidine

N,N-Dimethyl-5-methoxymethyl-2'-deoxycytidine

“…Thus, the orientation of the deoxyribose sugar ring and disruption of the hydrogen-bonding capacity of the N 4 group in N,N-dimethyl-MMdCyd provide insights for its inactivity. Although the exocyclic C5'--CH2OH side chain is in the favourable g÷ rotamer conformation (Gupta et al, 1987;Gupta et al, 1992;Jia et al, 1990a;Stuart et al, 1997), the 2T 3 twist conformation of the sugar ring results in negligible phosphorylation by the HSV-TK, and physiologically significant levels of the monophosphate are not formed in infected cells. In addition, the lack of the N 4 group's capacity to be a hydrogen-bond donor possibly inhibits interaction of the compound with the HSV-TK.…”