Synthesis and anti-influenza virus activity of 7-O-alkylated derivatives related to zanamivir.
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.
Honda
Takeshi
T
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. thonda@shina.sankyo.co.jp
Masuda
Takeshi
T
Yoshida
Shuku
S
Arai
Masami
M
Kaneko
Satoru
S
Yamashita
Makoto
M
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005995:Glyceryl Ethers / Q000737:chemistry* / Q000494:pharmacology*; D006146:Guanidines; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology; D020128:Inhibitory Concentration 50; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D011714:Pyrans; D012794:Sialic Acids / Q000737:chemistry*; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay; D053243:Zanamivir
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D005995:Glyceryl Ethers; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D053243:Zanamivir