title: 3-deaza- and 7-deaza-5'-noraristeromycin and their antiviral properties.
abstract: An enantiospecific synthesis of 3-deaza-5'-noraristeromycin as its dihydrochloride ((-)-6) has been accomplished in six steps beginning with the reaction of (+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate with 4-chloro-1H-imidazo[4,5-c]pyridine. The preparation of 7-deaza-5'-noraristeromycin ((-)-7) was described previously. Compounds (-)-6 and (-)-7 were evaluated for antiviral activity against a large number of viruses. Compound (-)-6 produced an antiviral activity pattern similar to 5'-noraristeromycin but was less potent. Compound (-)-6 inhibited CEM cell proliferation at a 50% inhibitory concentration of 27 micrograms/mL but proved not inhibitory to HEL cell proliferation and not toxic to E6SM, HeLa, Vero, and MDCK cells at concentrations up to 200 micrograms/mL. While (-)-6 showed inhibition of S-adenosyl-L-homocysteine (AdoHcy) hydrolase, it was less inhibitory than 5'-noraristeromycin. Compound (-)-7 displayed no antiviral properties or inhibitory effects toward AdoHcy hydrolase.
authors.affiliation: Department of Chemistry, University of South Florida, Tampa 33620.
authors.forename: S M
authors.initials: SM
authors.lastname: Siddiqi
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Rao
authors.forename: S W
authors.initials: SW
authors.lastname: Schneller
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.forename: R
authors.initials: R
authors.lastname: Snoeck
authors.forename: G
authors.initials: G
authors.lastname: Andrei
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D008745:Methylation; D051379:Mice; D008826:Microbial Sensitivity Tests; D013601:T-Lymphocytes / Q000187:drug effects; D014709:Vero Cells
chemical_list: C092762:3-deaza-5'-noraristeromycin; C092763:7-deaza-5'-noraristeromycin; D000998:Antiviral Agents; D000241:Adenosine