Molecular Diversity in Drug Design

• Συγγραφή απο Οργανισμό/Αρχή: SpringerLink (Online service)
• Άλλοι συγγραφείς: Dean, Philip M. (Επιμελητής έκδοσης), Lewis, Richard A. (Επιμελητής έκδοσης)
• Μορφή: Ηλεκτρονική πηγή Ηλ. βιβλίο
• Γλώσσα: English
• Έκδοση: Dordrecht : Springer Netherlands, 2002.
• Θέματα: Chemistry.; Pharmacy.; Chemoinformatics.; Chemistry, Physical and theoretical.; Computer Applications in Chemistry.; Theoretical and Computational Chemistry.

 High-throughput screening and combinatorial chemistry are two of the most potent weapons ever to have been used in the discovery of new drugs. At a stroke, it seems to be possible to synthesise more molecules in a month than have previously been made in the whole of the distinguished history of organic chemistry, Furthermore, all the molecules can be screened in the same short period. However, like any weapons of immense power, these techniques must be used with care, to achieve maximum impact. The costs of implementing and running high-throughput screening and combinatorial chemistry are high, as large dedicated facilities must be built and staffed. In addition, the sheer number of chemical leads generated may overwhelm the lead optimisation teams in a hail of friendly fire. Mother nature has not entirely surrendered, as the number of building blocks that could be used to build libraries would require more atoms than there are in the universe. In addition, the progress made by the Human Genome Project has uncovered many proteins with different functions but related binding sites, creating issues of selectivity. Advances in the new field of pharmacogenomics will produce more of these challenges. There is a real need to make hi- throughput screening and combinatorial chemistry into 'smart' weapons, so that their power is not dissipated. That is the challenge for modellers, computational chemists, cheminformaticians and IT experts. In this book, we have broken down this grand challenge into key tasks. 

 Issues in Molecular Diversity and the Role of Ligand Binding Sites -- Molecular Diversity in Drug Design. Application to High-speed Synthesis and High-Throughput Screening -- Background Theory of Molecular Diversity -- Absolute vs Relative Similarity and Diversity -- Diversity in Very Large Libraries -- Subset-Selection Methods For Chemical Databases -- Molecular Diversity in Site-focused Libraries -- Managing Combinatorial Chemistry Information -- Design of Small Libraries for Lead Exploration -- The Design of Small- and Medium-sized Focused Combinatorial Libraries.