title: Synthesis and in vitro anti-hepatitis B and C virus activities of ring-expanded ('fat') nucleobase analogues containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system.
abstract: As part of our structure-activity relationship studies, we report here the synthesis and in vitro anti-HBV and anti-HCV activities of a number of ring-expanded ('fat') nucleobases containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system. One of the compounds, ZP-88, exhibited a good activity/toxicity profile against HBV by inhibition of the synthesis of extracellular virion release (EC(50)=1.7microM, CC(50)=286microM, SI=168) and intracellular HBV replication intermediates (EC(50)=8.4microM, CC(50)=286microM, SI=34) in cultured human hepatoblastoma 2.2.15 cells. By contrast, most of the compounds tested against HCV had only marginal activity/toxicity profile, although that was still better than that of the reference compound ribavirin.
authors.affiliation: Laboratory for Drug Design and Synthesis, Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Brent E
authors.initials: BE
authors.lastname: Korba
authors.forename: Ramachandra S
authors.initials: RS
authors.lastname: Hosmane
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D006509:Hepatitis B / Q000188:drug therapy; D006515:Hepatitis B virus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D009705:Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D014771:Virion / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001552:Benzazepines; D007093:Imidazoles; D009705:Nucleosides