Fragment-based chemistry

Chemistry-based toxicity also involves exposure response, individual variability, and altered clearance. However, the proximal toxicant is typically a reactive chemical species. Several current systems are used for this purpose, such as mutagenicity (see Chapter 14) and carcinogenicity software programs, fragment-based chemistry and biology predictors, adduct determinations, and metabolite predictors. 

The editors have chosen topics from both important therapeutic areas and from work that advances the discipline of medicinal chemistry. For example, cancer, metabolic syndrome and Alzheimer s disease are fields in which academia and industry are heavily invested to discover new drugs because of their considerable unmet medical need. The editors have therefore prioritized covering new developments in medicinal chemistry in these fields. In addition, important advances in the discipline, such as fragment-based drug design and other aspects of new lead-seeking approaches, are also planned for early volumes in this series. Each volume thus offers a unique opportunity to capture the most up-to-date perspective in an area of medicinal chemistry. 

J. M. Blaney, V. Nienaber and S. K. Burley, Fragment-based lead discovery and optimization using X-ray crystallography, computational chemistry, and high throughput organic synthesis, in... 

Jahnke, W., Erlanson, D.A. (Eds) Fragment-Based Approaches in Drug Discovery. Vol 34 in series Methods and Principles in Medicinal Chemistry (Series Eds R. Mannhold, H. Kubinyi, G. Folkers). Weinheim, Germany Wiley-VCH 2006. 

Poulsen, S.-A. Bomaghi, L. F. Fragment-based drug discovery of carbonic anhydrase 11 inhibitors by dynamic combinatorial chemistry utilizing alkene cross metathesis. Bioorg. Med. Chem. 2006,14, 3275-3284. 

Poulsen, S.-A. Kruppa, G. Ft. In situ fragment-based medicinal chemistry Screening by mass spectrometry, hi Fragment-based drug discovery Practical aspects, Zartler, E. R., Shapiro, M. J. editors. Wiley, London, Chapter 7,2008. 

Ertl, P., Rohde, B. and Selzer, P. (2000) Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. Journal of Medicinal Chemistry, 43, 3714—3717. 

PRO SELECT Combines combinatorial chemistry and fragment-based docking methods to design structure-based libraries (75)... 

Gill, A. (2004). New lead generation strategies for protein-kinase inhibitors - fragment based screening approaches. Mini-Reviews in Medicinal Chemistry 4, 301-11. 

Villar, H. O., and Hansen, M. R. (2007). Computational techniques in fragment based drug discovery. Current Topics in Medicinal Chemistry 7, 1509-1513. 

Schuffenhauer, A., Ruedisser, S., Marzinzik, A. E., Jahnke, W., Blommers, M. J. J., Selzer, P, and Jacoby, E. (2005). Library design for fragment based screening. Current Topics in Medicinal Chemistry 5, 751-62. 

Hartshorn, M. J., Murray, C. W., Cleasby, A., Frederickson, M., Tickle, I. J., and Jhoti, H. (2005). Fragment-based lead discovery using X-ray crystallography. Journal of Medicinal Chemistry 48, 403—413. 

Chilli, A., Williams, G, Smith, A. G, Blundell, T. L and Abell, C. (2006). Probing hot spots at protein-ligand binding sites a fragment-based approach using biophysical methods. Journal of Medicinal Chemistry 49, 4992-4500. 

Geschwindner, S., Olsson, L. L., Albert, J. S., Deinum, J., Edwards, P. D., de Beer, T., and Folmer, R. H. A. (2007). Discovery of a novel warhead against beta-secretase through fragment-based lead generation. Journal of Medicinal Chemistry 50, 5903-5911. 

Alex, A. A., and Flocco, M. M. (2007). Fragment-based drug discovery what has it achieved so far Current Topics in Medicinal Chemistry 7, 1544—1567. 

Kolb, P., and Caflisch, A. (2006). Automatic and efficient decomposition of two-dimensional structures of small molecules for fragment-based high-throughput docking. Journal of Medicinal Chemistry 49, 7384-7392. 

D. A. Erlanson, M.D. Ballinger and J.A. Wells, Tethering, in Fragment-based Approaches in Drug Discovery (ed. W. Jahnke and D.A. Erlanson), Methods and Principles in Medicinal Chemistry, Vol. 34, Wiley-VCH Verlag GmbH, Weinheim, pp. 285-310 (2006). 

In Situ Fragment-based Medicinal Chemistry Screening by Mass Spectrometry... 

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