title: The use of ligand-based de novo design for scaffold hopping and sidechain optimization: two case studies.
abstract: This paper describes the application of de novo design utilizing exclusively ligand information. In the current approach, ligand design criteria, including pharmacophores, similarity and desired properties are applied as part of a fitness function driving the design process, instead of using them as filters after the process. This allows relevant parts of chemical space to be explored more efficiently. Two case studies of successful ligand design are also presented, one aimed at scaffold hopping, the other for exploring substitution patterns around a novel scaffold.
authors.affiliation: Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA. bosched@wyeth.com
authors.forename: Miklos
authors.initials: M
authors.lastname: Feher
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Gao
authors.forename: J Christian
authors.initials: JC
authors.lastname: Baber
authors.forename: William A
authors.initials: WA
authors.lastname: Shirley
authors.forename: John
authors.initials: J
authors.lastname: Saunders
mesh_terms: D000465:Algorithms; D017076:Computer-Aided Design; D015195:Drug Design; D006801:Humans; D008024:Ligands; D014179:Neurotransmitter Uptake Inhibitors; D011967:Receptors, Gonadotropin
chemical_list: D008024:Ligands; D014179:Neurotransmitter Uptake Inhibitors; D011967:Receptors, Gonadotropin