title: Synthesis and antiviral activities of new acyclic and "double-headed" nucleoside analogues.
abstract: To develop an understanding of the structure-activity relationships for the inhibition of orthopoxviruses by nucleoside analogues, a variety of novel chemical entities were synthesized. These included a series of pyrimidine 5-hypermodified acyclic nucleoside analogues based upon recently discovered new leads, and some previously unknown "double-headed" or "abbreviated" nucleosides. None of the synthetic products possessed significant activity against two representative orthopoxviruses; namely, vaccinia virus and cowpox virus. They were also devoid of significant activity against a battery of other DNA and RNA viruses. So far as the results with the orthopoxviruses and herpes viruses, the results may point to the necessity for nucleoside analogues 5'-phosphorylation for antiviral efficacy.
authors.affiliation: Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86011-5698, USA.
authors.forename: Xinying
authors.initials: X
authors.lastname: Zhang
authors.forename: Adel
authors.initials: A
authors.lastname: Amer
authors.forename: Xuesen
authors.initials: X
authors.lastname: Fan
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Mark
authors.initials: M
authors.lastname: Prichard
authors.forename: Earl
authors.initials: E
authors.lastname: Kern
authors.forename: Paul F
authors.initials: PF
authors.lastname: Torrence
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018155:Orthopoxvirus / Q000187:drug effects*; D012328:RNA Viruses / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides