کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1363336 981510 2010 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel pyrazolo-tetrahydropyridines as potent orexin receptor antagonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Novel pyrazolo-tetrahydropyridines as potent orexin receptor antagonists
چکیده انگلیسی

A novel series of dual orexin receptor antagonists was prepared by heteroaromatic five-membered ring system replacement of the dimethoxyphenyl moiety contained in the tetrahydroisoquinoline core skeleton of almorexant. Thus, replacement of the dimethoxyphenyl by a substituted pyrazole and additional optimization of the substitution pattern of the phenethyl motif allowed the identification of potent antagonists with low nanomolar affinity for hOX1R and hOX2R. The synthesis and structure–activity relationship of these novel antagonists will be discussed in this communication. These investigations furnished several suitable candidates for further evaluation in in vivo studies in rats.

A novel series of dual orexin receptor antagonists was prepared by heteroaromatic five-membered ring system replacement of the dimethoxyphenyl moiety contained in the tetrahydroisoquinoline core skeleton of almorexant, a dual orexin receptor antagonist in phase 3 clinical development.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 5, 1 March 2010, Pages 1539–1542
نویسندگان
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