Structural diversity and potency range distribution of scaffolds from compounds active against current pharmaceutical targets

Abstract

Aim: Large numbers of biologically active compounds are available from which scaffolds (core structures) can be isolated and compared focusing on structural, potency and promiscuity criteria.

Results: A computational analysis has been carried out to characterize all scaffolds and cyclic skeletons contained in currently available compounds from medicinal chemistry sources. Compounds active against hundreds of pharmaceutical targets were found to contain many structurally distinct scaffolds and cyclic skeletons. For given targets, these scaffolds often represent highly potent compounds.

Conclusion: There is an abundance of scaffold diversity among specifically active compounds indicating that many pharmaceutically relevant proteins are highly permissive small molecular targets. These findings have several implications for drug discovery and design.