Combinatorial chemistry and fragment screening--two unlike siblings?
Efficiently scouting the chemical space is one of the major challenges for lead discovery for drug development. In recent times some shifts have been made away from HTS and combinatorial chemistry to more focused approaches. Combinatorial chemistry was the starting point for the development of synthesis concepts that were intended to cover and explore the chemical space without having to prepare every individual compound. In this review, these lead finding approaches will be discussed comparing virtual and synthesized libraries. In addition we discuss the concepts and relationships of evolutionary libraries using genetic algorithms and dynamic combinatorial chemistries, as well as templated fragment ligation concepts. Taking a more abstract view of all approaches, the concepts may loop back into Combinatorial Chemistry allowing a more educated choice of building blocks and chemistries.
Aventis Pharma, Industrial Park Höchst G 879, 65926 Frankfurt, Germany. peter.nestler@aventis.com
Hans Peter
HP
Nestler
D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004345:Drug Industry; D010446:Peptide Fragments / Q000138:chemical synthesis; D019151:Peptide Library
D010446:Peptide Fragments; D019151:Peptide Library