3D Pharmacophore, hierarchical methods, and 5-HT₄ receptor binding data

Abstract

5-Hydroxytryptamine subtype-4 (5-HT₄) receptors have stimulated considerable interest amongst scientists and clinicians owing to their importance in neurophysiology and potential as therapeutic targets. A comparative analysis of hierarchical methods applied to data from one thousand 5-HT₄ receptor–ligand binding interactions was carried out. The chemical structures were described as chemical and pharmacophore fingerprints. The definitions of indices, related to the quality of the hierarchies in being able to distinguish between active and inactive compounds, revealed two interesting hierarchies with the Unity (1 active cluster) and pharmacophore fingerprints (4 active clusters). The results of this study also showed the importance of correct choice of metrics as well as the effectiveness of a new alternative of the Ward clustering algorithm named Energy (Minimum E-Distance method). In parallel, the relationship between these classifications and a previously defined 3D 5-HT₄ antagonist pharmacophore was established.

• 5-HT4
• antagonists
• pharmacophore
• clustering
• similarity

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.