2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2005 Dec 15;15(24):5397-401. doi: 10.1016/j.bmcl.2005.09.015.
Peng Zhang 1,  Ning Zhang,  Brent E Korba,  Ramachandra S Hosmane
Affiliations

Affiliation

  • 1 Laboratory for Drug Design and Synthesis, Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
PMID: 16213713 DOI: 10.1016/j.bmcl.2005.09.015
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.

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