Synthesis and in vivo influenza virus-inhibitory effect of ester prodrug of 4-guanidino-7-O-methyl-Neu5Ac2en

被引：39

作者：

Honda, Takeshi ^{[1
]}

Kubo, Shuku ^{[3
]}

Masuda, Takeshi ^{[2
]}

Arai, Masami ^{[1
]}

Kobayashi, Yoshiyuki ^{[4
]}

Yamashita, Makoto ^{[2
]}

机构：

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

[2] Daiichi Sankyo Co Ltd, Med Chem Res Labs 2, Edogawa Ku, Tokyo 1348630, Japan

[3] Daiichi Sankyo Co Ltd, Biol Res Labs 4, Shinagawa Ku, Tokyo 1408710, Japan

[4] Daiichi Sankyo Co Ltd, Global Project Management Dept, Shinagawa Ku, Tokyo 1408710, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 11期

关键词：

Ester prodrug; CS-8958; Zanamivir; Influenza; Long-acting NA inhibitor; NEURAMINIDASE INHIBITORS; 4-GUANIDINO-2,4-DIDEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC ACID; HIGHLY POTENT; SIALIDASE; ZANAMIVIR; GG167; ACID-6-PROPYLAMIDES; DERIVATIVES; DISCOVERY; DESIGN;

D O I：

10.1016/j.bmcl.2009.04.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of ester prodrugs of 7-O-methyl derivative of Zanamivir (compound 3) was synthesized and their efficacy was evaluated in an influenza infected mice model by intranasal administration. Compound 7c (CS-8958), octanoyl ester prodrug of the C-9 alcohol of compound 3, was found to be much longer-acting than Zanamivir. Furthermore, the in vivo efficacies of compounds 12a, 12b, and 12c, the linear alkyl ester prodrug of the carboxylic acid, were comparable to that exerted by compound 7c. (C) 2009 Published by Elsevier Ltd.

引用

页码：2938 / 2940

页数：3

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