کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10337210 692753 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
3D-QSAR comparative molecular field analysis on delta opioid receptor agonist SNC80 and its analogs
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
3D-QSAR comparative molecular field analysis on delta opioid receptor agonist SNC80 and its analogs
چکیده انگلیسی
Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) for a series of δ opioid receptor agonists: SNC80 analogs. Quantum chemical calculations on SNC80 show that protonation is preferred at the basic N4 atom over the alternative N1 atom, accordingly N4 protonation may contribute significantly to ligand-receptor interactions under physiologically relevant conditions. Statistically significant and predictive CoMFA models were achieved by pooling biological data from independent published sources, including compounds with both αR and αS benzylic configurations. Improved CoMFA models were obtained when the compounds were considered as N4-protonated species rather than neutral compounds. The influence of various atomic partial-charge formalisms, alignment schemes and additional molecular descriptors was evaluated in order to produce the highest quality models. In addition, separate CoMFA models were generated for compounds with only the αR benzylic configuration. These CoMFA models showed excellent internal predictability and consistency, and external validation using test-set compounds yielded predicted pIC50 values within 1 log unit of the corresponding experimentally measured values. Key insights into the structure-activity relationship derived from the CoMFA analysis concur with experimentally observed data, thus the CoMFA models presented here find utility for predicting the binding affinity, and guiding the design, of novel SNC80 analogs and related δ opioid receptor agonists.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Graphics and Modelling - Volume 24, Issue 1, September 2005, Pages 25-33
نویسندگان
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