title: Synthesis and in vitro anti-hepatitis B virus activity of six-membered azanucleoside analogues.
abstract: Fifteen novel six-membered azanucleoside derivatives were prepared and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in human hepatoblastoma-derived liver Hep-G2 cells. The most potent compound 16b with an IC(50) value of 2.74μg/mL (lower than 3TC) and a SI value of 13.5 was disclosed. The key synthetic steps involved the rearrangement of lactones (which were readily obtained from monosaccharides) and the Lewis acid-catalyzed condensation of nucleobases with azasugar donors. Using the versatile acetylated azasugar donors, azanucleosides covering three types of azasugars and four types of natural nucleobases were successfully obtained. The experimental results showed that some six-membered azanucleosides may find applications in the discovery of new anti-viral agents.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. No. 38, Beijing 100191, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Li
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Rong-Mei
authors.initials: RM
authors.lastname: Gao
authors.forename: Li-He
authors.initials: LH
authors.lastname: Zhang
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Ye
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000998:Antiviral Agents; D001372:Aza Compounds; D009705:Nucleosides