Fragment-based screening is now well-established as a powerful approach to early drug ("lead") discovery.
Some saturated heterocycles (and C-substitution patterns) are under-represented in the library (Fig.1; red and orange). The EubOpen set of 108 compounds was designed to address this lack of diversity. Additionally these additional compounds were carefully chosen to be compatible with a new range of reactions enabling expansions vectors that were previously not considered (fig 2).
Fig1. Carbon-substituted heterocycles are under-represented in the DSiP library
The DSI-P was designed to allow a quick enumeration of analogues by using conventional and well-known chemistry reactions. Novel reactions, in particular α-(het)arylation and β-functionalisation of saturated nitrogen heterocycles increase the number of “poised” positions for fragment growth. Adam Nelson and Steve Marsden at the University of Leeds have established a reaction toolkit to “grow” saturated cyclic amine fragments both α and β to N e.g. Chem. Eur. J. 2020, 26, 14861; Chem. Commun. 2020, 56, 8802.
The DSiP extension is provided by the EUbOPEN consortium and is available to all users.
SMILES: click to download the EUbOPEN DSiP extension plate map.
For follow-ups, please contact: Adam Nelson
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