title: Sulfonamide-related conformational effects and their importance in structure-based design.
abstract: Structure-based design (SBD) is a challenging endeavour since even localised SAR can hardly ever be explained by the variation of just one dominating factor. Here, we present a rare example where structural information combined with ab initio calculations clearly indicate that the observed difference in biological activity is dominated by conformational effects. The learnings discussed are successfully put to the test and have the potential to be of general use as a qualitative guide in SBD efforts.
authors.affiliation: GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. stefan.x.senger@gsk.com
authors.forename: Stefan
authors.initials: S
authors.lastname: Senger
authors.forename: Chuen
authors.initials: C
authors.lastname: Chan
authors.forename: Máire A
authors.initials: MA
authors.lastname: Convery
authors.forename: Julia A
authors.initials: JA
authors.lastname: Hubbard
authors.forename: Gita P
authors.initials: GP
authors.lastname: Shah
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Watson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Young
mesh_terms: D015195:Drug Design; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D013449:Sulfonamides