Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core

Gary T Wang; Sheldon Wang; Robert Gentles; Thomas Sowin; Clarence J Maring; Dale J Kempf; Warren M Kati; Vincent Stoll; Kent D Stewart; Graeme Laver

doi:10.1016/j.bmcl.2004.10.022

Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core

Bioorg Med Chem Lett. 2005 Jan 3;15(1):125-8. doi: 10.1016/j.bmcl.2004.10.022.

Authors

Gary T Wang¹, Sheldon Wang, Robert Gentles, Thomas Sowin, Clarence J Maring, Dale J Kempf, Warren M Kati, Vincent Stoll, Kent D Stewart, Graeme Laver

Affiliation

¹ Global Pharmaceutical Research & Development, Abbott Laboratories, Abbott Park, IL 60064, USA. [email protected]

PMID: 15582424
DOI: 10.1016/j.bmcl.2004.10.022

Abstract

(+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-methoxycarbonyl]tetrahydrofuran-5-carboxylic acid (9) and (+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-(4'-imidazolyl)]tetrahydrofuran 5-carboxylic acid (14) were synthesized as inhibitors of influenza neuraminidase (NA). Both compounds 9 and 14 inhibit influenza NA A with an IC(50) of about 0.5 microM and NA B with an IC(50) of 1.0 microM.

MeSH terms

Carboxylic Acids / chemistry*
Crystallography, X-Ray
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Furans / chemical synthesis
Furans / chemistry*
Furans / pharmacology
Models, Molecular
Molecular Structure
Neuraminidase / antagonists & inhibitors*
Orthomyxoviridae / enzymology*

Substances

Carboxylic Acids
Enzyme Inhibitors
Furans
Neuraminidase