Novel inhibitors of influenza sialidases related to GG167 - Structure-activity, crystallographic and molecular dynamic studies with 4H-pyran-2-carboxylic acid 6-carboxamides

被引：51

作者：

Smith, PW

Sollis, SL

Howes, PD

Cherry, PC

Cobley, KN

Taylor, H

Whittington, AR

Scicinski, J

Bethell, RC

Taylor, N

Skarzynski, T

Cleasby, A

Singh, O

Wonacott, A

Varghese, J

Colman, P

机构：

[1] GLAXO WELLCOME RES & DEV LTD,MED RES CTR,CORE COMBINATORIAL GRP,STEVENAGE SG1 2NY,HERTS,ENGLAND

[2] GLAXO WELLCOME RES & DEV LTD,MED RES CTR,DEPT ENZYME PHARMACOL,STEVENAGE SG1 2NY,HERTS,ENGLAND

[3] GLAXO WELLCOME RES & DEV LTD,MED RES CTR,DEPT BIOMOL STRUCT,STEVENAGE SG1 2NY,HERTS,ENGLAND

[4] BIOMOL RES INST,PARKVILLE,VIC,AUSTRALIA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 24期

关键词：

D O I：

10.1016/S0960-894X(96)00542-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The structure-activity relationships of a series of 4-amino and guanidino-4H-pyran-2-carboxylic acid 6-carboxamides are described. These compounds represent a new class of inhibitor of influenza sialidases and are particularly active against influenza A sialidase. The binding of the N-phenethyl-N-propylamide 4l to influenza A and B sialidases has been investigated using X-ray crystallography and molecular dynamics simulations. Our results suggest that formation of a hitherto unobserved intramolecular salt bridge within the enzymes may account for the observed activity and selectivity of the series. Copyright (C) 1996 Elsevier Science Ltd

引用

页码：2931 / 2936

页数：6

共 7 条

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