A Theoretical Study of the Relationships between Electronic Structure and 5-HT1A and 5-HT2A Receptor Binding Affinity of a group of ligands containing an isonicotinic nucleus

Abstract A formal quantum-chemical analysis of the relationships between the electronic structure of two series of isonicotinamide derivatives and their 5-HT_1A and 5-HT_1B receptor binding affinities was carried out. The electronic structure was calculated at the B3LYP/6-31G(d,p) after full geometry optimization. Statistically significant relationships were obtained for the four cases. The analysis of the results suggests what modifications of the molecules could be useful to raise receptor affinity. The partial 2D pharmacophores for the binding to each receptor suggest that both, 5-HT_1A and 5-HT_2A, seem to have a site that is rich in sigma electrons.

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