Synthesis and anti-influenza virus activity of 4-guanidino-7-substituted Neu5Ac2en derivatives.
Substitution of 7-OH by small hydrophobic groups on zanamivir resulted in the retaining of low nanomolar inhibitory activities against not only influenza A virus sialidase but also influenza A virus in cell culture. These compounds were prepared by treatment of the corresponding 7-substituted sialic acids derived from 4-modified N-acetyl-D-mannosamine (ManNAc) using enzyme-catalyzed aldol condensation.
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
Kobayashi
Yoshiyuki
Y
Yamashita
Makoto
M
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology; D009981:Influenza B virus / Q000187:drug effects* / Q000201:enzymology; D020128:Inhibitory Concentration 50; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D019791:Guanidine