The molecular structure and the dynamic behaviour of some potent 5-HT3 antagonists structurally related to quipazine have been investigated by NMR spectroscopy and by computational methods in order to gain insight into the structure-activity relationships at a molecular level. The role of the different dynamic behaviour of these compounds in the binding to 5-HT3 receptors is discussed. A model of ligand-receptor interaction has been developed on the basis of molecular orbital calculations and on the reference ligands quipazine, ondansetron and LY278584. The interaction model proposed herein rationalizes the observed agonist-antagonist shift between quipazine and investigated compounds with the assumption of different but overlapping binding domains for antagonists and agonists at the 5-HT3 receptor. Copyright
Molecular structure and dynamics of some potent 5-HT3 receptor antagonists. Insight into the interaction with the receptor / Cappelli, A; Donati, A; Anzini, M; Vomero, S; DE BENEDETTI, Pier Giuseppe; Menziani, Maria Cristina; Langer, T.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 4:(1996), pp. 1255-1269.