Quantitative structure-activity relationship study on affinity profile of a series of 1,8-naphthyridine antagonists toward bovine adenosine receptors

The affinity profiles for the bovine adenosine receptors, A1 and A2A, of a series of 1,8-naphthyridine derivatives were quantitatively analyzed using physicochemical and structural parameters of the substituents, present at varying positions of the molecules. The derived significant correlation, for bovine A1 receptor, suggested that a R1 substituent having a higher van der Waals volume, a R2 substituent being a hydrogen-bond donor and a R3 substituent able to transmit a higher field effect are helpful in augmenting the pKi of a compound. Similarly the study, pertaining to bovine A2A receptor, revealed that a less bulky substituent at R2 and a strong electron-withdrawing substituent at R3 are desirable in improving the binding affinity of a compound while substituents at R1 remain insignificant to any interaction.