Study of the bioactive conformation of novel 5-HT4 receptor ligands: influence of an intramolecular hydrogen bond

By using NMR and IR techniques and theoretical methods, we have studied the prototropic equilibrium present in the benzimidazole ring of a series of derivatives acting at serotonin 5-HT4 receptors. The structural study has allowed us to get insight into the bioactive conformation of the novel 5-HT4 receptor ligands which has been supported by biological data. This will help the docking of the ligands into a 3-D model of the receptor binding site in order to guide the design and synthesis of new compounds with predetermined pharmacological activities.