title: Recent developments in de novo design and scaffold hopping.
abstract: 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.
authors.affiliation: F Hoffmann-La Roche Ltd, Discovery Chemistry, 4070 Basel, Switzerland. harald.mauser@roche.com
authors.forename: Harald
authors.initials: H
authors.lastname: Mauser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Guba
mesh_terms: 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*
chemical_list: D008024:Ligands; D054852:Small Molecule Libraries