کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1370127 981809 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rational design and synthesis of aminopiperazinones as β-secretase (BACE) inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Rational design and synthesis of aminopiperazinones as β-secretase (BACE) inhibitors
چکیده انگلیسی

Aminopiperazinone inhibitors of BACE were identified by rational design. Structure based design guided idea prioritization and initial racemic hit 18a showed good activity. Modification in decoration and chiral separation resulted in the 40 nM inhibitor, (−)-37, which showed in vivo reduction of amyloid beta peptides. The crystal structure of 18a showed a binding mode driven by interaction with the catalytic aspartate dyad and distribution of the biaryl amide decoration towards S1 and S3 pockets.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 24, 15 December 2011, Pages 7255–7260
نویسندگان
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