Structure-based drug design of chromone antagonists of the adenosine A 2A receptor

The structure-guided optimisation of a hit series of chromone derivatives, previously identified using virtual screening of homology models of the adenosine A 2A receptor, has led to the discovery of potent, selective and ligand efficient antagonists. Lipophilic hotspots and calculated water networks were modelled within the receptor binding site to facilitate rational ligand design.