title: Acyclic nucleoside phosphonates with a branched 2-(2-phosphonoethoxy)ethyl chain: efficient synthesis and antiviral activity.
abstract: Series of novel acyclic nucleoside phosphonates (ANPs) with various nucleobases and 2-(2-phosphonoethoxy)ethyl (PEE) chain bearing various substituents in β-position to the phosphonate moiety were prepared. The influence of structural alternations on antiviral activity was studied. Several derivatives exhibit antiviral activity against HIV and vaccinia virus (middle micromolar range), HSV-1 and HSV-2 (lower micromolar range) and VZV and CMV (nanomolar range), although the parent unbranched PEE-ANPs are inactive. Adenine as a nucleobase and the methyl group attached to the PEE chain proved to be a prerequisite to afford pronounced antiviral activity.
authors: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ-16610 Prague 6, Czech Republic. lasice@uochb.cas.cz
authors: Dana
authors: D
authors: Hocková
authors: Antonín
authors: A
authors: Holý
authors: Graciela
authors: G
authors: Andrei
authors: Robert
authors: R
authors: Snoeck
authors: Jan
authors: J
authors: Balzarini
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy; D006561:Herpes Simplex / Q000188:drug therapy; D006801:Humans; D051379:Mice; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014615:Vaccinia / Q000188:drug therapy; D014616:Vaccinia virus / Q000187:drug effects; D014777:Virus Diseases / Q000188:drug therapy; D014780:Viruses / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates