An efficient, short synthesis and potent anti-hepatitis B viral activity of a novel ring-expanded purine nucleoside analogue containing a 5:7-fused, planar, aromatic, imidazo[4,5-e][1,3]diazepine ring system.
An efficient, short synthesis of a ring-expanded nucleoside analogue containing a novel 5:7-fused, planar, and potentially aromatic imidazo[4,5-e][1,3]diazepine heterocyclic ring system is reported. The target compound, 6-amino-8-hydroxy-4H-1-beta-D- ribofuranosylimidazo[4,5-e][1,3]diazepin-4-one (2) was synthesized in a single step in > or = 90% yield by condensation of guanidine with either methyl 1-beta-D-ribofuranosylimidazole-4,5- dicarboxylate(1a) or its 2',3',5'-tri-O-benzoyl derivative (1b). Compound 2 showed potent anti-hepatitis B virus (anti-HBV) activity with an EC50 value of 0.17 microM in the transfected hepatoma cell line 2.2.15, and a low cellular toxicity with a CC50 value of 2.4 mM (TI > 14,000).
Chen
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HM
Department of Chemistry & Biochemistry, University of Maryland, Baltimore County (UMBC) 21250, USA.
Sood
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Hosmane
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RS
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D002470:Cell Survival / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
C119902:6-amino-8-hydroxy-4H-1-ribofuranosylimidazo(4,5-e)(1,3)diazepin-4-one; D000998:Antiviral Agents; D001381:Azepines; D011684:Purine Nucleosides