Molecular Modeling Studies Focused on 5-HT7 versus 5-HT1A Selectivity. Discovery of Novel Phenylpyrrole Derivatives with High Affinity for 5-HT7 Receptors
Journal of Chemical Information and Modeling2005Vol. 45(4), pp. 1075–1081
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Alban Lepailleur, Ronan Bureau, Magalie Paillet‐Loilier, Frédéric Fabis, Nicolas Saettel, Stéphane Lemaître, François Dauphin, Aurélien Lesnard, Jean‐Charles Lancelot, Sylvain Rault
Abstract
The present study discusses the well-known 5-HT7/5-HT1A selectivity issue through a new series of phenylpyrrole derivatives. The first hits emerged from a virtual screening performed on a chemolibrary. Further study led to an optimization of a preliminary 5-HT7 pharmacophore model. The importance of each pharmacophoric feature is confirmed, but these characteristics have to be coupled to geometric constraints in order to achieve a 5-HT7 selectivity. Indeed, 5-HT1A affinity probably arises from extended conformations, whereas a bent one appears to be best suited for 5-HT7 selectivity.
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