Journal
CHEMICAL SOCIETY REVIEWS
Volume 41, Issue 12, Pages 4444-4456Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2cs35023h
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Funding
- European Union
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council
- Medical Research Council
- Frances and Augustus Newman Foundation
- Wellcome Trust
- Isaac Newton Trust
- German Academic Exchange Service (DAAD)
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Small molecule modulators of biological function can be discovered by the screening of compound libraries. However, it became apparent that some human disease related targets could not be addressed by the libraries commonly used which typically are comprised of large numbers of structurally similar compounds. The last decade has seen a paradigm shift in library construction, with particular emphasis now being placed on increasing a library's structural, and thus functional diversity, rather than only its size. Diversity-oriented synthesis (DOS) aims to generate such structural diversity efficiently. This tutorial review has been written to introduce the subject to a broad audience and recent achievements in both the preparation and the screening of structurally diverse compound collections against so-called 'undruggable' targets are highlighted.
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