title: QSAR studies and pharmacophore identification for arylsubstituted cycloalkenecarboxylic acid methyl esters with affinity for the human dopamine transporter.
abstract: Data from a series of 29 monoamine transport inhibitors were used to generate 2D and 3D QSAR models for their binding affinity to the human dopamine transporter (hDAT). Among the inhibitors were many non-nitrogen containing compounds. The 2D QSAR analysis resulted in the equation -logK(i)=4.00-3.93E(LUMO)-0.67E(HOMO)-3.24sigma(p), which predicted the importance of electron withdrawing groups in the aromatic moiety. However, the model failed to predict the observed poor binding of nitro-substituted compounds. In contrast, a derived 3D QSAR model was capable of predicting these more correctly.
authors.affiliation: Department of Chemistry, University of Aarhus, Langelandsgade 140, Aarhus C, Denmark.
authors.forename: Helena S
authors.initials: HS
authors.lastname: Christensen
authors.forename: Søren V
authors.initials: SV
authors.lastname: Boye
authors.forename: Jacob
authors.initials: J
authors.lastname: Thinggaard
authors.forename: Steffen
authors.initials: S
authors.lastname: Sinning
authors.forename: Ove
authors.initials: O
authors.lastname: Wiborg
authors.forename: Birgit
authors.initials: B
authors.lastname: Schiøtt
authors.forename: Mikael
authors.initials: M
authors.lastname: Bols
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D003198:Computer Simulation; D003516:Cycloparaffins / Q000737:chemistry* / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D003516:Cycloparaffins; D050483:Dopamine Plasma Membrane Transport Proteins