The authors were interested in the heterocyclic ring system produced by the three component Groebke-Blackburn-Bienaymé reaction as a possible pharmaceutical scaffold. They designed and synthesized a library of substituted products, and solved the structure of one to confirm its structural properties. CSD-CrossMiner was used to identify binding patterns (as it is seen both in their obtained crystal structure and the literature), to find similar structural motifs in the PDB and generate new ideas for further lead optimization and scaffold hopping.
The ability to scaffold hop, that is to change a structure whilst retaining the key features which make it biologically active, allows medicinal chemists to design possible alternatives. This may be to improve the pharmacology or specificity.
The authors used CSD-CrossMiner to define a pharmacophore search done by defining the key features essential to the molecule's function, and then mining for results which fulfil these features. This returned 37 cocrystal structures, demonstrating additional potential future scaffolds.
Read the European Journal of Organic Chemistry paper here.
Learn more about CSD-CrossMiner here.
Explore more examples of CCDC tools in action here.
Download the Infographic CrossMiner: Drug Discovery through Data Mining