Synthesis and antiviral properties of carbocyclic 3'-oxa-2',3'-dideoxyguanosine and its 7-deazaguanosine analogue.
To evaluate analogues of the antiviral agent (R)-9-(3,4-dihydroxybutyl)guanine in which the side-chain C-3 hydroxyl oxygen is part of a five-membered ring, carbocyclic 3'-oxa-2',3'-dideoxyguanosine (4) and carbocyclic 3'-oxa-2',3'-dideoxy-7-deazaguanosine (5) have been synthesized in 17 and 14 steps, respectively, from 5-O-acetyl-1,2-O-isopropylidene-alpha-D-xylofuranose. Compounds 4 and 5 and their 6-chloro precursors were evaluated against a wide variety of DNA and RNA viruses. Only 4 showed any marginal activity and this was limited to HSV-1 and HSV-2. Even though 4 was less potent towards these latter two viruses than acyclovir, its mechanism and target of action is proposed to resemble that of acyclovir. The only toxicity observed for these compounds was observed in the cell growth assay with human embryonic lung cells.
Chen
X
X
Department of Chemistry, University of South Florida, Tampa 33620-5250.
Siddiqi
S M
SM
Schneller
S W
SW
Snoeck
R
R
Balzarini
J
J
De Clercq
E
E
D000212:Acyclovir / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D008826:Microbial Sensitivity Tests; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C080961:carbocyclic 3'-oxa-2',3'-dideoxyguanosine; C080962:carbocyclic 3'-oxa-2',3'-dideoxy-7-deazaguanosine; D000212:Acyclovir