کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10588121 | 981445 | 2011 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structure-guided design and synthesis of P1â² position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Previously, we reported potent pentapeptidic BACE1 inhibitors with the hydroxymethylcarbonyl isostere as a substrate transition-state mimic. To improve the in vitro potency, we further reported pentapeptidic inhibitors with carboxylic acid bioisosteres at the P4 and P1â² positions. In the current study, we screened new P1â² position 1-phenylcycloalkylamine analogs to find non-acidic inhibitors that possess double-digit nanomolar range IC50 values. An extensive structure-activity relationship study was performed with various amine derivatives at the P1â² position. The most potent inhibitor of this pentapeptide series, KMI-1830, possessing 1-phenylcyclopentylamine at the P1â² position had an IC50 value of 11.6Â nM against BACE1 in vitro enzymatic assay.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 17, 1 September 2011, Pages 5238-5246
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 17, 1 September 2011, Pages 5238-5246
نویسندگان
Harichandra D. Tagad, Yoshio Hamada, Jeffrey-Tri Nguyen, Koushi Hidaka, Takashi Hamada, Youhei Sohma, Tooru Kimura, Yoshiaki Kiso,