title: Synthesis and antiviral activities of hexadecyloxypropyl prodrugs of acyclic nucleoside phosphonates containing guanine or hypoxanthine and a (S)-HPMP or PEE acyclic moiety.
abstract: Hexadecyloxypropyl esters of acyclic nucleoside phosphonates containing guanine (G) or hypoxanthine (Hx) and a (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] [(S)-HPMP] or 2-(2-phosphonoethoxy)ethyl (PEE) acyclic moiety have been prepared. The activity of the prodrugs was evaluated in vitro against different virus families. Whereas ester derivatives of PEEHx and (S)-HPMPHx were antivirally inactive, monoesters of PEEG, and mono- and diesters of (S)-HPMPG showed pronounced antiviral activity against vaccinia virus and/or herpesviruses. Monoesters of (S)-HPMPG emerged as the most potent and selective derivatives against these DNA viruses. None of the compounds were inhibitory against RNA viruses and retroviruses.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, Prague 166 10, Czech Republic. tichy78@uochb.cas.cz
authors.forename: Tomáš
authors.initials: T
authors.lastname: Tichý
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Martin
authors.initials: M
authors.lastname: Dračínský
authors.forename: Marcela
authors.initials: M
authors.lastname: Krečmerová
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D004267:DNA Viruses / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006801:Humans; D019271:Hypoxanthine / Q000737:chemistry*; D007042:Hypoxanthines / Q000737:chemistry*; D009705:Nucleosides / Q000737:chemistry*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010757:Phosphorous Acids / Q000737:chemistry*; D011355:Prodrugs / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D007042:Hypoxanthines; D009705:Nucleosides; D063065:Organophosphonates; D010757:Phosphorous Acids; D011355:Prodrugs; D019271:Hypoxanthine; D006147:Guanine