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.

Graphical abstractAn example is presented where structural information combined with ab initio calculations clearly indicate that an observed difference in biological activity is dominated by sulfonamide-related conformational effects.Figure optionsDownload full-size imageDownload as PowerPoint slide