title: Synthesis and antiviral activity of certain second generation methylenecyclopropane nucleosides.
abstract: A second-generation series of substituted methylenecyclopropane nucleosides (MCPNs) has been synthesized and evaluated for antiviral activity against a panel of human herpesviruses, and for cytotoxicity. Although alkylated 2,6-diaminopurine analogs showed little antiviral activity, the compounds containing ether and thioether substituents at the 6-position of the purine did demonstrate potent and selective antiviral activity against several different human herpesviruses. In the 6-alkoxy series, antiviral activity depended on the length of the ether carbon chain, with the optimum chain length being about four carbon units long. For the corresponding thioethers, compounds containing secondary thioethers were more potent than those with primary thioethers.
authors.affiliation: Microbiotix, Inc., One Innovation Drive, Worcester, MA 01605, USA. jwilliams@microbiotix.com
authors.forename: John D
authors.initials: JD
authors.lastname: Williams
authors.forename: Atiyya R
authors.initials: AR
authors.lastname: Khan
authors.forename: Emma A
authors.initials: EA
authors.lastname: Harden
authors.forename: Caroll B
authors.initials: CB
authors.lastname: Hartline
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Jefferson
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Keith
authors.forename: Mark N
authors.initials: MN
authors.lastname: Prichard
authors.forename: Jiri
authors.initials: J
authors.lastname: Zemlicka
authors.forename: Norton P
authors.initials: NP
authors.lastname: Peet
authors.forename: Terry L
authors.initials: TL
authors.lastname: Bowlin
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000821:virology; D006564:Herpesviridae / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D009705:Nucleosides; C508672:methylenecyclopropane