Synthesis and anti-influenza evaluation of polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives.
We synthesized polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en analogues on the polyglutamic acid back bone, via a spacer of alkyl ether at the C-7 position. These multivalent conjugates 9 and 10 showed enhancement of antiviral activity against infuenza A virus and more potent efficacy in vivo relative to a monomeric sialidase inhibitor.
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. thonda@shina.sankyo.co.jp
Takeshi
T
Honda
Shuku
S
Yoshida
Masami
M
Arai
Takeshi
T
Masuda
Makoto
M
Yamashita
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000737:chemistry; D005995:Glyceryl Ethers / Q000737:chemistry; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006146:Guanidines; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology; D020128:Inhibitory Concentration 50; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D011714:Pyrans; D012794:Sialic Acids; 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; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D018698:Glutamic Acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D019791:Guanidine; D053243:Zanamivir