Design, synthesis, and biological activity of thiazole derivatives as novel influenza neuraminidase inhibitors.

Abstract

A series of novel influenza neuraminidase (NA) inhibitors based on thiazole core were synthesized and evaluated for their ability to inhibit NA of influenza A virus (H(3)N(2)). All compounds were synthesized in good yields starting from commercially available 2-amino-4-thiazole-acetic ester using a suitable synthetic strategy. These compounds showed moderate inhibitory activity against influenza A NA. The most potent compound of this series is compound 4d (IC(50) = 3.43 μM), which is about 20-fold less potent than oseltamivir, and could be used to design novel influenza NA inhibitors that exhibit increased activity based on thiazole ring.

• Authors: Yu Liu, Lei Zhang, Jianzhi Gong, Hao Fang, Ailin Liu, Guanhua Du, Wenfang Xu
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 26 Issue 4 Pg. 506-13 (Aug 2011) ISSN: 1475-6374 [Electronic] England
• PMID: 21143042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Enzyme Inhibitors
• Thiazoles
• Neuraminidase

Topics

• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Drug Design
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Influenza A Virus, H3N2 Subtype (enzymology)
• Microbial Sensitivity Tests
• Models, Molecular
• Molecular Structure
• Neuraminidase (antagonists & inhibitors, metabolism)
• Stereoisomerism
• Thiazoles (chemical synthesis, chemistry, pharmacology)