Synthesis and anti-influenza evaluation of orally active bicyclic ether derivatives related to zanamivir.

Abstract

We synthesized bicyclic ether sialidase inhibitors such as tetrahydro-furan-2-yl, tetrahydro-pyran-2-yl, and oxepan-2-yl derivatives related to zanamivir. These compounds substituted by diol at the C-3' and C-4' positions resulted in the retention of low nanomolar inhibitory activities against not only influenza A virus sialidase but also influenza A virus in cell culture. Compound 11a in particular showed comparable efficacy in vivo relative to that of oseltamivir phosphate.

• Authors: Takeshi Masuda, Satoshi Shibuya, Masami Arai, Shuku Yoshida, Takanori Tomozawa, Akiko Ohno, Makoto Yamashita, Takeshi Honda
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 13 Issue 4 Pg. 669-73 (Feb 24 2003) ISSN: 0960-894X [Print] England
• PMID: 12639555 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Bridged Bicyclo Compounds, Heterocyclic
• Enzyme Inhibitors
• Ethers
• Guanidines
• Pyrans
• Sialic Acids
• Neuraminidase
• Zanamivir

Topics

• Administration, Oral
• Animals
• Antiviral Agents (chemistry, pharmacokinetics, pharmacology)
• Bridged Bicyclo Compounds, Heterocyclic (chemistry, pharmacokinetics, pharmacology)
• Drug Evaluation, Preclinical
• Enzyme Inhibitors (chemistry, pharmacokinetics, pharmacology)
• Ethers (chemistry, pharmacokinetics, pharmacology)
• Guanidines
• Influenza A virus (drug effects, enzymology)
• Inhibitory Concentration 50
• Mice
• Models, Molecular
• Molecular Conformation
• Neuraminidase (antagonists & inhibitors)
• Orthomyxoviridae Infections (drug therapy)
• Pyrans
• Sialic Acids (chemistry, pharmacokinetics, pharmacology)
• Structure-Activity Relationship
• Zanamivir