Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
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Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors Bearing 4-Guanidino-Neu5Ac2en Derivatives
Takeshi MasudaShuku YoshidaMasami AraiSatoru KanekoMakoto YamashitaTakeshi Honda
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2003 Volume 51 Issue 12 Pages 1386-1398


Polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives on a poly-L-glutamine backbone are described. Aiming for a longer retention time of 4-guanidino-Neu5Ac2en (zanamivir) in bronchi and lungs, we focused on supermolecules bearing 4-guanidino-Neu5Ac2en derivatives bound at their C-7 position through noncleavable alkyl ether linkages. We first found that alkylation of the 7-hydroxyl group of sialic acid derivative 8 proceeded smoothly, and produced 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives 13, which exhibited equipotent inhibitory activity against not only influenza A virus sialidase but also influenza A virus in the cell culture. Next, we synthesized poly-L-glutamine bearing 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives linked by amide bonds, 26, which showed enhanced antiviral activity against influenza A virus and more potent efficacy in vivo relative to a monomeric sialidase inhibitor.

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© 2003 The Pharmaceutical Society of Japan
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