title: Design, synthesis, and biological evaluation of new 2'-deoxy-2'-fluoro-4'-triazole cytidine nucleosides as potent antiviral agents.
abstract: A series of 4'-[1,2,3]triazole-2'-deoxy-2'-fluoro-β-d-arabinofuranosylcytosines (9-17) were prepared by Cu(I)-mediated [3 + 2] cycloaddition reactions (CuAAC) of 1-(4'-azido-2'-deoxy-2'-fluoro-β-d-arabinofuranosyl)cytosine (1) with appropriate alkynes in good yields. Their structures were fully established by (1)H NMR, (13)C NMR, HRMS, and elemental analysis. Most of these nucleoside analogs exhibited potent anti-HIV-1 activity with no cytotoxicity observed at the highest tested concentration up to 25 μM. Among them, compounds 9, 10 and 13 exhibited extremely potent antiviral activity, thus had a great potential for further development as novel nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV-1 infection. Besides, the anti-HBV activity of compounds 10, 11 and 17 had been investigated.
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Wenquan
authors.initials: W
authors.lastname: Yu
authors.forename: Leixia
authors.initials: L
authors.lastname: Fu
authors.forename: Wu
authors.initials: W
authors.lastname: He
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Baoshan
authors.initials: B
authors.lastname: Chai
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Song
authors.forename: Junbiao
authors.initials: J
authors.lastname: Chang
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003562:Cytidine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D015497:HIV-1 / Q000187:drug effects*; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D014230:Triazoles; D003562:Cytidine