Sulfonamide-related conformational effects and their importance in structure-based design.
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.
Senger
Stefan
S
GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. stefan.x.senger@gsk.com
Chan
Chuen
C
Convery
Máire A
MA
Hubbard
Julia A
JA
Shah
Gita P
GP
Watson
Nigel S
NS
Young
Robert J
RJ
D015195:Drug Design; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology
D013449:Sulfonamides