title: Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries.
abstract: Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural similarity. Several such potential scaffolds for combinatorial chemistry were identified that are not present in current trade drugs. For one of these scaffolds a virtual combinatorial library was generated. Pharmacophoric properties of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs and natural products have several topological pharmacophore patterns in common. These features can be systematically explored with selected combinatorial libraries based on a combination of natural product-derived and synthetic molecular building blocks.
authors.affiliation: F. Hoffmann-La Roche, Ltd., Pharmaceuticals Division, CH-4070 Basel, Switzerland.
authors.forename: M L
authors.initials: ML
authors.lastname: Lee
authors.forename: G
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000465:Algorithms; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D006571:Heterocyclic Compounds; D004364:Pharmaceutical Preparations