کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1358881 981371 2015 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Boronic acid-containing CXCR1/2 antagonists: Optimization of metabolic stability, in vivo evaluation, and a proposed receptor binding model
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Boronic acid-containing CXCR1/2 antagonists: Optimization of metabolic stability, in vivo evaluation, and a proposed receptor binding model
چکیده انگلیسی

Blockade of undesired neutrophil migration to sites of inflammation remains an area of substantial pharmaceutical interest. To effect this blockade, a validated therapeutic target is antagonism of the chemokine receptor CXCR2. Herein we report the discovery of 6-(2-boronic acid-5-trifluoromethoxy-benzylsulfanyl)-N-(4-fluoro-phenyl)-nicotinamide 6, an antagonist with activity at both CXCR1 and CXCR2 receptors (IC50 values 31 and 21 nM, respectively). Compound 6 exhibited potent inhibition of neutrophil influx in a rat model of pulmonary inflammation, and is hypothesized to interact with a unique intracellular binding site on CXCR2. Compound 6 (SX-576) is undergoing further investigation as a potential therapy for pulmonary inflammation.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 25, Issue 11, 1 June 2015, Pages 2280–2284
نویسندگان
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