title: Synthesis and antiviral evaluation of novel 2',2'-difluoro 5'-norcarbocyclic phosphonic acid nucleosides as antiviral agents.
abstract: A very efficient synthetic route to novel 2',2'-difluoro 5'-norcarbocyclic phosphonic acid nucleosides from but-3-en-1-ol 5 is described. The discovery of 2'-fluorinated furanose nucleoside 1 as a potent anti-HIV-1 agent has led to the synthesis and biological evaluation of 2'-modified 5'-norversions of the carbocyclic phosphonate nucleosides. The synthesized nucleoside analogues 18, 19, 23a, 23b, and 24 were tested for anti-HIV activity as well as cytotoxicity. Adenine analogue 19 shows significant anti-HIV-1 activity (EC(50) = 13 μM).
authors.affiliation: a BK-21 Project Team, College of Pharmacy , Chosun University , Kwangju , Republic of Korea.
authors.forename: Guang Huan
authors.initials: GH
authors.lastname: Shen
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D063065:Organophosphonates / Q000138:chemical synthesis*; D010757:Phosphorous Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: C000592621:9-((4-hydroxymethyl-2',2'-difluorocyclopentan-1'-yl)adenine)phosphonic acid; D019380:Anti-HIV Agents; D009705:Nucleosides; D063065:Organophosphonates; D010757:Phosphorous Acids; C570063:phosphonic acid; D000241:Adenosine