SYNTHESIS OF 6-CARBON, 7-CARBON AND 8-CARBON SUGAR ANALOGS OF POTENT ANTIINFLUENZA 2,3-DIDEHYDRO-2,3-DIDEOXY-N-ACETYLNEURAMINIC ACID-DERIVATIVES

被引:58
作者
BAMFORD, MJ
PICHEL, JC
HUSMAN, W
PATEL, B
STORER, R
WEIR, NG
机构
[1] Glaxo Research and Development Limited, Medicines Research Centre, Stevenage, Hertfordshire, SG1 2NY, Gunnels Wood Road
来源
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 | 1995年 / 09期
关键词
D O I
10.1039/p19950001181
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Analogues of the potent anti-influenza A and B compound, 4-guanidino-Neu5Ac2en, are described in which the stereochemically demanding C-6-glycerol side-chain is truncated. Syntheses of the one- and two-carbon side-chain analogues, of both 4-guanidino- and 4-amino-Neu5Ac2en, are presented, as well as the syntheses of analogues lacking any side-chain. Whilst complete removal of the C-6 side-chain abolishes activity, a stepwise increase in inhibition of influenza neuraminidase and influenza A and B in cell culture with increasing C-6 chain length is observed. The one-carbon, hydroxymethyl derivative retains significant activity to represent a suitable lead in the search for neuraminidase inhibitors of reduced stereochemical demand and synthetic complexity.
引用
收藏
页码:1181 / 1187
页数:7
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