title: Synthesis and antiviral evaluation of cis-substituted cyclohexenyl and cyclohexanyl nucleosides.
abstract: Starting from commercially available (rac)-3-cyclohexene-1-carboxylic acid, a series of purine and pyrimidine cis-substituted cyclohexenyl and cyclohexanyl nucleosides were synthesized through a key Mitsunobu reaction. Antiviral evaluations were performed on HIV, coxsackie B3, and herpes viruses (HSV-1, HSV-2, VZV, HCMV). Three compounds showed moderate activity against HSV-1 and coxsackie viruses. Specific computer modeling studies were performed on HSV-1 thymidine kinase in order to understand the enzyme activation of an analogue showing moderate antiviral activity.
authors.affiliation: Laboratoire des Matériaux Moléculaires et des Biomatériaux, GCOM2, UMR CNRS 6114, Université de la Méditerranée, case 901, 163 av. de Luminy, 13288 Marseille Cedex 9, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Barral
authors.forename: Jérôme
authors.initials: J
authors.lastname: Courcambeck
authors.forename: Gérard
authors.initials: G
authors.lastname: Pèpe
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: Michel
authors.initials: M
authors.lastname: Camplo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects; D029822:Enterovirus B, Human / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014616:Vaccinia virus / Q000187:drug effects; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D003510:Cyclohexanes; D009705:Nucleosides