Synthesis and antiviral activity of acyclic nucleosides with a 3(S),5-dihydroxypentyl or 4(R)-methoxy-3(S),5-dihydroxypentyl side chain.
Optically pure acyclic nucleoside analogues with a 3(S),5-dihydroxypentyl or 4(R)-methoxy-3(S),5-dihydroxypentyl side chain were synthesized starting from 2-deoxy-D-ribose. The acyclic nucleosides were obtained by alkylation of the bases with the mesylates 16 and 17. Of these series of novel nucleoside analogues only 9-[3(S),5-dihydroxypent-1-yl]guanine (6d) showed marked antiviral activity. It inhibited the cytopathogenicity of herpes simplex virus type 1 (HSV-1) at a concentration of 0.4-0.6 microgram/mL, which thus points to a greater antiviral activity than recently reported for the mixture of the R and S enantiomers (12.5 micrograms/mL). In contrast with 6d, its 4(R)-methoxy derivative 7d did not show antiviral activity, which implies that the 4'-methoxy group is unable to mimic the 1',4'-oxygen bridge of the normal furanose ring.
Vandendriessche
F
F
Laboratory of Pharmaceutical Chemistry, Katholieke Universiteit Leuven, Leuven, Belgium.
Snoeck
R
R
Janssen
G
G
Hoogmartens
J
J
Van Aerschot
A
A
De Clercq
E
E
Herdewijn
P
P
D000998:Antiviral Agents / Q000138:chemical synthesis*; D008826:Microbial Sensitivity Tests; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D009705:Nucleosides