Structure-based drug design of chromone antagonists of the adenosine A2A 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.