Recent developments in de novo design and scaffold hopping.
This review covers the developments in the fields of de novo ligand design and scaffold hopping since 2006. De novo ligand design was introduced in 1991 as a purely structure-based method to suggest ligands for synthesis and was later augmented by ligand-based approaches. Both structure-based and ligand-based methods identify pharmacophores, as well as shape constraints, and subsequently match these with complementary features embedded into small-molecule topologies. Recently, significant attention has been paid to de novo ligand design in combination with biophysical fragment screening and X-ray structure elucidation. Scaffold hopping has evolved from a niche application of de novo design into a rapidly expanding suite of different software tools, which are used extensively in the pharmaceutical industry.
Mauser
Harald
H
F Hoffmann-La Roche Ltd, Discovery Chemistry, 4070 Basel, Switzerland. harald.mauser@roche.com
Guba
Wolfgang
W
D000818:Animals; D003196:Computer Graphics; D003198:Computer Simulation; D017076:Computer-Aided Design; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods*
D008024:Ligands; D054852:Small Molecule Libraries