کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1362495 | 981489 | 2010 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1′ and P4 positions
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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 of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1′ and P4 positions Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1′ and P4 positions](/preview/png/1362495.png)
چکیده انگلیسی
We previously reported potent BACE1 inhibitors KMI-420 and KMI-570 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Acidic moieties at the P1′ and P4 positions of KMI inhibitors are thought to be unfavorable in terms of membrane permeability across the blood–brain barrier. Herein, we replaced acidic moieties at the P4 position with hydrogen bond accepting groups and acidic moieties at the P1′ position with less acidic and similar molecular-size moieties (carboxylic acid or tetrazole bioisosteres). These inhibitors exhibited improved BACE1 inhibitory activities and a thorough quantitative structure–activity relationship study was performed.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 9, 1 May 2010, Pages 3175–3186
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 9, 1 May 2010, Pages 3175–3186
نویسندگان
Harichandra D. Tagad, Yoshio Hamada, Jeffrey-Tri Nguyen, Takashi Hamada, Hamdy Abdel-Rahman, Abdellah Yamani, Ayaka Nagamine, Hayato Ikari, Naoto Igawa, Koushi Hidaka, Youhei Sohma, Tooru Kimura, Yoshiaki Kiso,