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 recogniti on have been successfully applied to explain the binding affinities of a se ries of benzimidazole derivatives 1-24 acting at serotonin 5-HT(4)Rs. Both derived computational models have facilitated the identification of the str uctural elements of the ligands that are key to high 5-HT4R affinity. The r esults 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. (C) 2001 Elsevier Science Ltd. All rights reser ved.