Receptor-based 3D QSAR analysis of serotonin 5-HT1D receptor agonists

Abstract

A three-dimensional quantitative structure - activity relationship study (3D QSAR) has been successfully applied to explain the binding affinities for the serotonin 5-HT1D receptor of a triptan series. The paper describes the development of a receptor-based 3D QSAR model of some known agonists and recently developed triptans on the 5-HT1D serotonergic receptor, showing a significant correlation between predicted and experimentally measured binding affinity (pIC(50)). The pIC(50) values of these agonists are in the range from 5.40 to 9.50. The ligand alignment obtained from dynamic simulations was taken as basis for a 3D QSAR analysis applying the GRID/GOLPE program. 3D QSAR analysis of the ligands resulted in a model of high quality (r(2) = 0.9895, q(LOO)(2) = 0.7854). This is an excellent result and proves both the validity of the proposed pharmacophore and the predictive quality of the 3D QSAR model for the triptan series of serotonin 5-HT1D receptor agonists.