|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|1368675||981706||2016||3 صفحه PDF||ندارد||دانلود رایگان|
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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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 14, 15 July 2016, Pages 3213–3215