Journal article
Novel inhibitors of influenza sialidases related to GG167. Structure-activity, crystallographic and molecular dynamics studies with 4H-pyran-2-carboxylic acid 6-carboxamides
PW Smith, SL Sollis, PD Howes, PC Cherry, KN Cobley, H Taylor, AR Whittington, J Scicinski, RC Bethell, N Taylor, T Skarzynski, A Cleasby, O Singh, A Wonacott, J Varghese, P Colman
Bioorganic and Medicinal Chemistry Letters | Published : 1996
Abstract
The structure-activity relationship 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 41 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.