Synthesis and anti-Influenza virus activity of 7- O-Alkylated derivatives related to zanamivir

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 15; pp. 1925 - 1928
• Main Authors: Honda, Takeshi, Masuda, Takeshi, Yoshida, Shuku, Arai, Masami, Kaneko, Satoru, Yamashita, Makoto
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 05.08.2002; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; Biological and medical sciences; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Glyceryl Ethers - chemistry; Glyceryl Ethers - pharmacology; Guanidines; Influenza A virus - drug effects; Influenza A virus - enzymology; Inhibitory Concentration 50; Medical sciences; N-Acetylneuraminic Acid - chemistry; Neuraminidase - antagonists & inhibitors; Pharmacology. Drug treatments; Pyrans; Sialic Acids - chemistry; Structure-Activity Relationship; Viral Plaque Assay; Zanamivir; Enzyme; Enzyme inhibitor; Orthomyxoviridae; Aldonic acid; In vitro; Zanamivir; Virus; Influenzavirus A; Structure activity relation; Influenza A virus; Glycosidases; Aminoglycoside; Exo-α-sialidase; Hydrolases; Antiviral; Chemical synthesis; O-Glycosidases; Ethylenic compound
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00329-3

A series of 7-alkyl ether derivatives related to zanamivir were synthesized using direct alkylation of the C-7 alcohol of sialic acid. Alkyl ether moiety of less than 12 carbons in length showed low nanomolar inhibitory activity against influenza A virus sialidase. Furthermore, their moiety improved influenza A virus plaque reduction activity compared to zanamivir. However, removal of the 8,9-diol of the 7- O-alkyl derivatives resulted in loss of antiviral potency. This result suggests that 8,9-diol must play an important role in binding with both influenza A and B virus sialidases. Graphic