title: Synthesis and evaluation of novel 6',6'-difluoro 5'-deoxycarbocyclic phosphonic acid nucleosides as antiviral agents.
abstract: The authors describe highly efficient synthetic routes for the preparation of novel 6',6'-difluoro 5'-deoxycarbocyclic phosphonic acid nucleosides from 1,4-dihydroxy-2-butene. The discovery that the 6'-fluorinated carbocyclic nucleoside (2, EC₅₀ = 0.16 μM) is a potent anti-HSV-1 agent led to the syntheses and biological evaluations of 6'-modified 5'-deoxyversions of carbocyclic phosphonate nucleosides. The synthesized nucleoside analogues 15, 18, 22, and 25 were tested for anti-HIV activity and for cytotoxicity. However, none of them showed significant anti-HIV-1 activity or cytotoxicity at concentrations up to 100 μM.
authors.affiliation: BK-21 Project Team, College of Pharmacy, Chosun University, Kwangju 501-759, Republic of Korea.
authors.forename: Eunae
authors.initials: E
authors.lastname: Kim
authors.forename: Guang Huan
authors.initials: GH
authors.lastname: Shen
authors.forename: Lien
authors.initials: L
authors.lastname: Kang
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D054879:Halogenation; D006801:Humans; D008958:Models, Molecular; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010757:Phosphorous Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D010757:Phosphorous Acids; C570063:phosphonic acid