title: The conformational musings of a medicinal chemist.
abstract: Structure-based drug design strategies based on X-ray crystallographic data of ligands bound to biological targets or computationally derived pharmacophore models have been introduced over the past 25 years or so. These have now matured and are deeply embedded in the drug discovery process in most pharmaceutical and biotechnology companies where they continue to play a major part in the discovery of new medicines and drug candidates. Newly developed NMR methods can now provide a full description of the conformations in which ligands exist in free solution, crucially allowing those that are dominant to be identified. Integrating experimentally determined conformational information on active and inactive molecules in drug discovery programmes, alongside the existing techniques, should have a major impact on the success of drug discovery.
authors.affiliation: The Coach House, Grenville Court, Britwell Road, Burnham, Slough SL1 8DF, UK; Unit 310 Ducie House, Ducie Street, Manchester M1 2JW, UK. Electronic address: harry.finch@pulmagen.com.
authors.forename: Harry
authors.initials: H
authors.lastname: Finch
mesh_terms: D001709:Biotechnology / Q000379:methods / Q000639:trends; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D004345:Drug Industry / Q000379:methods / Q000639:trends; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands