Towards drugging the ‘undruggable’: enhancing the scaffold diversity of synthetic small molecule screening collections using diversity-oriented synthesis

• Authors: Warren R.J.D. Galloway , David R. Spring
• Languages of publication: EN

Abstracts

EN

Medicinal chemistry research has traditionally focused upon a limited set of biological targets. Many other human disease-related targets have been termed ‘undruggable’ as they have proved largely impervious to modulation by small molecules. However, it is becoming increasingly evident that such targets can indeed be modulated; they are simply being challenged with the wrong types of molecules. Traditionally, screening libraries were composed of large numbers of structurally similar compounds. However, library size is not everything; the structural diversity of the library, which is largely dictated by the range of molecular scaffolds present, is crucial. Diversity-oriented synthesis (DOS) generates small molecule libraries with high levels of scaffold, and thus structural, diversity. Such collections should provide hits against a broad range of targets with high frequency, including ‘undruggable’ targets. Examples in the area of scaffold diversity generation taken from the author’s laboratories are given.

Keywords

EN

Diversity-oriented synthesis; Undruggable targets; Antibacterials

• Publisher: De Gruyter Open
• Journal: Diversity Oriented Synthesis
• Year: 2012
• Volume: 1
• Issue: 1

Dates

received

12 - 1 - 2013

online

28 - 2 - 2013

accepted

4 - 2 - 2013

Contributors

author

Warren R.J.D. Galloway

• Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK

author

David R. Spring

• Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK

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Identifiers

DOI

10.2478/dos-2013-0001