QSAR studies and pharmacophore identification for arylsubstituted cycloalkenecarboxylic acid methyl esters with affinity for the human dopamine transporter.
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.
Christensen
Helena S
HS
Department of Chemistry, University of Aarhus, Langelandsgade 140, Aarhus C, Denmark.
Boye
Søren V
SV
Thinggaard
Jacob
J
Sinning
Steffen
S
Wiborg
Ove
O
Schiøtt
Birgit
B
Bols
Mikael
M
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
D002264:Carboxylic Acids; D003516:Cycloparaffins; D050483:Dopamine Plasma Membrane Transport Proteins