کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
1368675 981706 2016 3 صفحه PDF ندارد دانلود رایگان
عنوان انگلیسی مقاله
Novel JAK1-selective benzimidazole inhibitors with enhanced membrane permeability
ترجمه فارسی عنوان
مهارکننده های جدید benzimidazole JAK1 انتخابی با نفوذپذیری غشاء بهبودیافته
کلمات کلیدی
کیناز ادم؛ آرتریت روماتوئید؛ Benzimidazole؛ مهار انتخابی
Janus kinase; Rheumatoid arthritis; Benzimidazole; Selective inhibition
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی

The previously identified Janus kinase 1 (JAK1)-selective inhibitor, 1-(2-aminoethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole-5-carboxamide (2), suffered from low cell permeability, which resulted in poor pharmacokinetic properties. In this study, by introducing less polar hydrogen bond donors at N1 (a hydroxyalkyl or a methylaminoalkyl group) and C2 (a cyclohexanol group) positions, a series of novel benzimidazole derivatives were prepared, which exhibited selective JAK1 inhibitory activity (IC50 against JAK1 = 0.08–0.15 μM; JAK1-selectivity = 26–40 fold vs JAK2, 12–23 fold vs JAK3, and 38–54 fold vs Tyk2) along with significantly increased lipophilicity (3.3–15.8 times) as well as membrane permeability (6.3–12 times).

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 14, 15 July 2016, Pages 3213–3215
نویسندگان
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