کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1379388 | 982027 | 2005 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Trifluoroethylamines as amide isosteres in inhibitors of cathepsin K
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
The P2-P3 amide of dipeptide cathepsin K inhibitors can be replaced by the metabolically stable trifluoroethylamine group. The non-basic nature of the nitrogen allows the important hydrogen bond to Gly66 to be made. The resulting compounds are 10- to 20-fold more potent than the corresponding amide derivatives. Compound 8 is a 5 pM inhibitor of human cathepsin K with >10,000-fold selectivity over other cathepsins.
Replacing an amide bond with a trifluoroethylamine leads to potent and selective inhibitors of cathepsin K. The CF3 group provides a non-basic amine that makes a good hydrogen bond with the enzyme active site.Figure optionsDownload as PowerPoint slide
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 21, 1 November 2005, Pages 4741–4744
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 21, 1 November 2005, Pages 4741–4744
نویسندگان
W. Cameron Black, Christopher I. Bayly, Dana E. Davis, Sylvie Desmarais, Jean-Pierre Falgueyret, Serge Léger, Chun Sing Li, Frédéric Massé, Daniel J. McKay, James T. Palmer, M. David Percival, Joël Robichaud, Nancy Tsou, Robert Zamboni,