title: Synthesis and antiviral activity of 6-deoxycyclopropavir, a new prodrug of cyclopropavir.
abstract: Synthesis of 6-deoxycyclopropavir (10), a prodrug of cyclopropavir (1) and its in vitro and in vivo antiviral activity is described. 2-Amino-6-chloropurine methylenecyclopropane 13 was transformed to its 6-iodo derivative 14 which was reduced to prodrug 10. It is converted to cyclopropavir (1) by the action of xanthine oxidase and this reaction can also occur in vivo. Compound 10 lacked significant in vitro activity against human cytomegalovirus (HCMV), human herpes virus 1 and 2 (HSV-1 and HSV-2), human immunodeficiency virus type 1 (HIV-1), human hepatitis B virus (HBV), Epstein-Barr virus (EBV), vaccinia virus and cowpox virus. In contrast, prodrug 10 given orally was as active as cyclopropavir (1) reported previously [Kern, E. R.; Bidanset, D. J.; Hartline, C. B.; Yan, Z.; Zemlicka, J.; Quenelle, D. C. et al. Antimicrob. Agents Chemother. 2004, 48, 4745] against murine cytomegalovirus (MCMV) infection in mice and against HCMV in severe combined immunodeficient (SCID) mice.
authors.affiliation: Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201-1379, USA.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Li
authors.forename: Debra C
authors.initials: DC
authors.lastname: Quenelle
authors.forename: Mark N
authors.initials: MN
authors.lastname: Prichard
authors.forename: John C
authors.initials: JC
authors.lastname: Drach
authors.forename: Jiri
authors.initials: J
authors.lastname: Zemlicka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D015608:Cowpox virus / Q000187:drug effects; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D014616:Vaccinia virus / Q000187:drug effects
chemical_list: C574567:6-deoxycyclopropavir; D000998:Antiviral Agents; D003521:Cyclopropanes; D011355:Prodrugs; D006147:Guanine