کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1373056 981888 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Proline bis-amides as potent dual orexin receptor antagonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Proline bis-amides as potent dual orexin receptor antagonists
چکیده انگلیسی

A series of OX2R/OX1R dual orexin antagonists was prepared based on a proline bis-amide identified as a screening lead. Through a combination of classical and library synthesis, potency enhancing replacements for both amide portions were discovered. N-methylation of the benzimidazole moiety within the lead structure significantly reduced P-gp susceptibility while increasing potency, giving rise to good brain penetration. A compound from this series has demonstrated in vivo central activity when dosed peripherally in a pharmacodynamic model of orexin activity.

A series of potent dual orexin antagonists was prepared based on a proline bis-amide core that demonstrate in vivo central activity in a pharmacodyamic model of orexin activity.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 4, 15 February 2008, Pages 1425–1430
نویسندگان
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