3-D-QSAR/CoMFA and recognition models of benzimidazole derivatives at the 5-HT4 receptor

3-D-QSAR/CoMFA methodology and computational simulation of ligand recognition have been successfully applied to explain the binding affinities of a series of benzimidazole derivatives 1–24 acting at serotonin 5-HT4Rs. Both derived computational models have facilitated the identification of the structural elements of the ligands that are key to high 5-HT4R affinity. The results provide the tools for predicting the affinity of related compounds, and for guiding the design and synthesis of new ligands with predetermined affinities and selectivity.