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Quantitative Structure-Affinity Relationships of Dopamine D2 Receptor Antagonists: A Comparison between Orthopramides and 6-Methoxysalicylamides
Authors:Tomas de Paulis  Nabil El Tayar  Pierre-Alain Carrupt  Bernard Testa  Han van de Waterbeemd
Abstract:A large series of orthopramides (= 2-methoxybenzamides), 6-methoxysalicylamides, and 2,6-dimethoxy-benzamides were examined for their affinity to the dopamine D2 receptor. The binding data were correlated with physicochemical parameters and 13C-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-ethylpyrroIidin-2-yl)methyl] and N-(1-benzylpiperidin-4-yl) side-chains affect the mode of binding of these compounds.
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