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

100%

Galloway W. R. J. D. , Spring D. R.

Diversity Oriented Synthesis

2012

tom 1

nr 1

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.

Switchable multicomponent heterocyclizations for diversity oriented synthesis

75%

Chebanov V. A. , Desenko S. M.

Diversity Oriented Synthesis

2012

tom 1

nr 1

The present comprehensive review1 contains the analysis of literature data concerning switchable multicomponent heterocyclizations and demonstrates the application of these types of reactions to solve the matters of Diversity Oriented Synthesis.