Synthesis and anti-influenza virus activity of 7-O-alkylated derivatives related to zanamivir

被引：66

作者：

Honda, T

Masuda, T

Yoshida, S

Arai, M

Kaneko, S

Yamashita, M

机构：

[1] Sankyo Co Ltd, Med Chem Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[2] Sankyo Co Ltd, Biol Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(02)00329-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：1925 / 1928

页数：4

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