کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1373850 981908 2006 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Improved 3D-QSAR CoMFA of the dopamine transporter blockers with multiple conformations using the genetic algorithm
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Improved 3D-QSAR CoMFA of the dopamine transporter blockers with multiple conformations using the genetic algorithm
چکیده انگلیسی

A 3D-QSAR/CoMFA was performed for a series of 42 piperidine-based dopamine transporter (DAT) blockers. The overall process consisted of three major steps: (1) a pharmacophore model was built using the Genetic Algorithm Similarity Program (GASP); (2) the Flexible Superposition (FlexS) technique was applied to generate multiple conformations for each of the ligands based on the pharmacophore; (3) the Genetic Algorithm was employed to optimize the selection of the ligand conformations for the CoMFA modeling. The CoMFA models were found to be more detailed in the putative binding site by exploring multiple conformations of each ligand. The comparison of the contour maps shows that, in general, these models are comparable and the differences between them result from the ability of the flexible 3α-substituents of the ligands to adopt multiple conformations satisfying the same pharmacophore model. These findings provide guidance for the design and improvement of compounds with DAT activity, which is important for the development of a treatment of cocaine addiction and certain neurological disorders.

Multiple conformations of the ligands with the flexible 3α-substituent satisfy the same pharmacophore model.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 24, 15 December 2006, Pages 6267–6272
نویسندگان
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