title: Molecular modeling studies focused on 5-HT7 versus 5-HT1A selectivity. Discovery of novel phenylpyrrole derivatives with high affinity for 5-HT7 receptors.
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.
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, Université de Caen, U.F.R. des Sciences Pharmaceutiques, 5 rue Vaubénard, 14032 Caen Cedex, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Lepailleur
authors.forename: Ronan
authors.initials: R
authors.lastname: Bureau
authors.forename: Magalie
authors.initials: M
authors.lastname: Paillet-Loilier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fabis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Saettel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lemaître
authors.forename: François
authors.initials: F
authors.lastname: Dauphin
authors.forename: Aurélien
authors.initials: A
authors.lastname: Lesnard
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lancelot
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
mesh_terms: D019992:Databases as Topic; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry*; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: C400160:3-methyl-4-phenylpyrrole; D011758:Pyrroles; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A