A large series of orthopramides (= 2-methoxybenzamides), 6-methoxysalicylamides, and 2,6-dimethoxybenzamides were examined for their affinity to the dopamine D2 receptor. The binding data were correlated with physicochemical parameters and C-13-NMR chemical shifts using the cross-validated partial least-squares method and multiple linear regression analysis. The results quantitate the influence of electronic factors and lipophilicity to D2 receptor binding. They also show that the N-[(1-ethylpyrrolidin-2-yl)methyl] and N-(1-benzylpiperidin-4-yl) side-chains affect the mode of binding of these compounds