title: Enhancing a CH-π Interaction to Increase the Affinity for 5-HT1A Receptors.
abstract: An electrostatic interaction related to a favorable position of the distal phenyl ring and a phenylalanine residue in the binding pocket would explain the higher 5-HT1A affinity of a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue compared to the corresponding 4-phenylpiperazine analogue. To explore a possible reinforcement of this interaction to increase the affinity for 5-HT1A receptors, different 4-substituted-phenyl analogues were synthesized and tested. The most important increase of affinity is obtained with two electron-donating methyl groups in positions 3 and 5.
authors.affiliation: Laboratory of Medicinal Chemistry and C.I.R.M., University of Liège , avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Liégeois
authors.affiliation: Laboratory of Medicinal Chemistry and C.I.R.M., University of Liège , avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Lespagnard
authors.affiliation: Laboratory of Medicinal Chemistry and C.I.R.M., University of Liège , avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.
authors.forename: Elsa
authors.initials: E
authors.lastname: Meneses Salas
authors.affiliation: Laboratory of Medicinal Chemistry and C.I.R.M., University of Liège , avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.
authors.forename: Floriane
authors.initials: F
authors.lastname: Mangin
authors.affiliation: Laboratory of Pharmacology and GIGA-Neuroscience, University of Liège , avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Scuvée-Moreau
authors.affiliation: Laboratory of Medicinal Chemistry and C.I.R.M., University of Liège , avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium ; Laboratory of Pharmacology and GIGA-Neuroscience, University of Liège , avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dilly
keywords: CH−π interaction; arylpiperazine; carboxamide; docking; electron-donating; quinoxaline