ABSTRACT
Analogs of (E)-5-(2-bromovinyl)-2'-deoxycytidine (BrVdCyd) (1) by substitution at N(4) were synthesized to impart resistance against deamination. The anti-HSV-1 activity and solution conformation of these analogs were determined. N(4)-Acetyl-BrVdCyd (2) was a potent inhibitor of HSV-1 replication whereas N(4)-propanoyl-BrVdCyd (3) had good activity and N(4)-Butanoyl-BrVdCyd (4) had only low activity against HSV-1 replication. N(4)-Methyl-BrVdCyd (5) was devoid of activity against HSV-1.
Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Bromodeoxycytidine/analogs & derivatives , Simplexvirus/drug effects , Antiviral Agents/chemical synthesis , Bromodeoxycytidine/chemistry , Bromodeoxycytidine/pharmacology , Carbohydrate Conformation , Cell Line , Drug Stability , Humans , Microbial Sensitivity Tests , Virus Replication/drug effectsABSTRACT
Analogs of 5-methoxymethyl-2'-deoxycytidine, MMdCyd (1) by substitution at N4 were synthesized to impart resistance against deamination. The anti HSV-1 activity and solution conformation of analogs were determined. N4-Butanoyl-MMdCyd (10) was a potent inhibitor of HSV-1 replication while N4-hexanoyl-MMdCyd (11), N4-propanoyl-MMdCyd (9) and N4-acetyl-MMdCyd (8) had good activity against HSV-1 replication. All other analogs were devoid of activity against HSV-1.
