Abstract
Fraction sp3 (Fsp3) 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 Fsp3 values 0.45. These non-flat scaffolds may cover 83 % of ring systems that are absent from screening set.
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