The inhibitory effect of compounds 5-22 on the P2Y12R was determined utilizing a competitive radioligand binding assay following a modified protocol by Dupuis et al. with [ 33 P]2-MeSADP, a commercially available P2Y12R radioligand, as competitor (Table , Figure ). Compounds 5 and 6 were included to compare IC50 values with reported values from literature (Figure ). Many compounds show a good to moderate affinity for the receptor, with the most potent ligand being AZD1283 5 (IC50 = 51 nM) directly followed by 12 (IC50 = 79 nM) and 14 (IC50 = 199 nM). Compounds with a nitrile substituent were more affine than the compounds with chloride or hydrogen substituents, which confirms the prediction from previous docking experiments. Compounds 13 and 19 with the highest predicted affinity for the receptor in silico, showed the weakest interaction in the binding assay (17750 and 27140 nM). Thus, replacing the pyridyl with an aryl was not suitable given the observed reduction in affinity, although a potential interfering contribution of the propoxy group at position 4 has to be taken into account.