Scaffold Flatness: Reversing the Trend

Fraction sp 3 (Fsp 3) values were used to compare the flatness of known scaffolds (used as privileged structures, drug scaffolds, and in scaffold-hopping approaches) and natural product (NP) scaffolds. The vast majority of the known synthetic scaffolds are planar with Fsp 3 values 0.45. These non-flat scaffolds may cover 83 % of ring systems that are absent from screening set.