QSAR studies and pharmacophore identification for arylsubstituted cycloalkenecarboxylic acid methyl esters with affinity for the human dopamine transporter

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• 作者：Helena S. Christensen ; Sø ; ren V. Boye ; Jacob Thinggaard ; Steffen Sinning ; Ove Wiborg ; Birgit Schiø ; tt ; Mikael Bols
• 关键词：Monoamine transporters ; QSAR ; Inhibitors
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2007
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 August 2007
• 卷：15
• 期：15
• 页码：5262-5274
• 文件大小：364 K

摘要

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 −log K_i = 4.00 − 3.93E_LUMO − 0.67E_HOMO − 3.24σ_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.