title: A new pharmophoric model for 5-HT reuptake-inhibitors: differentiation of amphetamine analogues.
abstract: A pharmacophoric model for 5-HT reuptake-inhibitors was developed using the pharmacophore elements geometry and MEP (Molecular Electrostatic Potential) by the method of active analogue approach. This model is characterized by: (1) a protonated basic nitrogen separated by 610 pm from the center of an aromatic system and 920 pm from an electronegative substituent of this aromatic system, (2) a region with n- and/or pi-electrons along the axis substituent-aromatic system-nitrogen atom, (3) an aliphatic side chain which joins the region of the n- and/or pi-electrons with the nitrogen atom, (4) an additional aromatic group at right angles to the pharmacophoric aromatic group below the protonated nitrogen and (5) a forbidden region on the pharmacophore which leads to a deviation of the allowed tubular orientation of the ligand. The pharmacophore model enables a differentiation of the entactogenic, hallucinogenic and stimulating arylalkanamines. The theoretical considerations are confirmed by a postulated intramolecular H-bonding in the active conformation of the selective 5-HT reuptake-inhibitor, citalopram (12 in Fig. 2), which could be proved by NMR- and IR-spectroscopic measurements.
authors.affiliation: Pharmazeutisches Institut, Universität Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Rupp
authors.forename: K A
authors.initials: KA
authors.lastname: Kovar
authors.forename: G
authors.initials: G
authors.lastname: Beuerle
authors.forename: C
authors.initials: C
authors.lastname: Ruf
authors.forename: G
authors.initials: G
authors.lastname: Folkers
mesh_terms: D000662:Amphetamines / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000662:Amphetamines; D017367:Selective Serotonin Reuptake Inhibitors