کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1374706 | 981923 | 2006 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Design and synthesis of potent β-secretase (BACE1) inhibitors with P1′ carboxylic acid bioisosteres
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Design and synthesis of potent β-secretase (BACE1) inhibitors with P1′ carboxylic acid bioisosteres Design and synthesis of potent β-secretase (BACE1) inhibitors with P1′ carboxylic acid bioisosteres](/preview/png/1374706.png)
چکیده انگلیسی
Recently, we reported potent and small-sized β-secretase (BACE1) inhibitors KMI-420 and KMI-429 in which we replaced the Glu residue at the P4 position of KMI-260 and KMI-360, respectively, with a 1H-tetrazole-5-carbonyl DAP (l-α,β-diaminopropionic acid) residue. At the P1′ position, these compounds contain one or two carboxylic acid groups, which are unfavorable for crossing the blood–brain barrier. Herein, we report BACE1 inhibitors with P1′ carboxylic acid bioisosteres in order to develop practical anti-Alzheimer’s disease drugs. Among them, tetrazole ring-containing compounds, KMI-570 (IC50 = 4.8 nM) and KMI-684 (IC50 = 1.2 nM), exhibited significantly potent BACE1 inhibitory activities.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 9, 1 May 2006, Pages 2380–2386
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 9, 1 May 2006, Pages 2380–2386
نویسندگان
Tooru Kimura, Yoshio Hamada, Monika Stochaj, Hayato Ikari, Ayaka Nagamine, Hamdy Abdel-Rahman, Naoto Igawa, Koushi Hidaka, Jeffrey-Tri Nguyen, Kazuki Saito, Yoshio Hayashi, Yoshiaki Kiso,