In , 0.83% 48 and 100% . However, the lack of novelty of de novo designs is often criticised , hence here we show the nearest known A 2A ligand, training set compound, and vendor library compound in the supporting information. Moreover, we test and discover a diverse range of different chemotypes compared to some reported hit rates which only explore one chemotype , provide full dose response curves, a selectivity analysis versus A 2B receptor, and co-crystallise the two most potent binders to inform future iterations of structure-based design.