کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1365691 981570 2007 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of novel and orally active NR2B-selective N-methyl-d-aspartate (NMDA) antagonists, pyridinol derivatives with reduced HERG binding affinity
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery of novel and orally active NR2B-selective N-methyl-d-aspartate (NMDA) antagonists, pyridinol derivatives with reduced HERG binding affinity
چکیده انگلیسی

Novel NR2B antagonists with an amide tether were found by an approach to avoid pharmacophoric similarity to dofetilide. Structure–activity relationship investigation led to N-[cis-4-hydroxy-4-(5-hydroxypyridin-2-yl)cyclohexyl]-3-henylpropanamide 14e as an orally active NR2B-subtype selective N-methyl-d-aspartate (NMDA) receptor antagonist with very weak HERG (human ether-a-go-go related gene) binding (IC50 > 30 μM). This compound exhibited potent in vivo anti-allodynic activity in the mouse partial sciatic nerve ligation (PSL) model (minimum effective dose = 10 mg/kg, po).

Structure–activity relationship investigation led to N-[cis-4-hydroxy-4-(5-hydroxypyridin-2-yl)cyclohexyl]-3-phenylpropanamide 14e as an orally active NR2B-subtype selective N-methyl-d-aspartate (NMDA) receptor antagonist with very weak HERG binding (IC50 > 30 μM).Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 20, 15 October 2007, Pages 5533–5536
نویسندگان
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