title: Phosphoramidate protides of carbocyclic 2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine with potent activity against HIV and HBV.
abstract: Synthesis of phosphoramidate protides of carbocyclic D- and L-2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine by treatment of the nucleoside with phosphorochloridates in the presence of pyridine and t-BuMgCl is described. Several of these protides showed significantly improved antiviral potency over the parent nucleosides against both HIV and HBV.
authors.affiliation: Division of Chemistry, GlaxoSmithKline, Research Triangle Park, North Carolina, USA. Kristjan.S.Gudmundsson@gsk.com
authors.forename: Kristjan S
authors.initials: KS
authors.lastname: Gudmundsson
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Susan M
authors.initials: SM
authors.lastname: Daluge
authors.forename: Lance C
authors.initials: LC
authors.lastname: Johnson
authors.forename: Richard
authors.initials: R
authors.lastname: Hazen
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Condreay
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006678:HIV / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D015394:Molecular Structure; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: C500098:2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine; D000577:Amides; D000998:Antiviral Agents; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D000241:Adenosine; D014372:Tubercidin