Receptor-Based 3D QSAR Analysis of Serotonin 5-HT1D Receptor Agonists

A three-dimensional quantitative structure-activity relationship study (3D QSAR) has been successfully applied to explain the binding affinities for the serotonin 5-HT 1 D receptor of a triptan series. The paper describesthe development of a receptor-based 3D QSAR model of some known agonists and recently developed triptans on the 5-HT 1 D serotonergic receptor, showing a significant correlation between predicted and experimentally measured binding affinity (pIC 5 0 ). The pIC 5 0 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 2 L O O = 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-HT 1 D receptor agonists.

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