کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10588598 | 981485 | 2011 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Quinolones as HCV NS5B polymerase inhibitors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Hepatitis C virus (HCV) infection is treated with a combination of peginterferon alfa-2a/b and ribavirin. To address the limitations of this therapy, numerous small molecule agents are in development, which act by directly affecting key steps in the viral life-cycle. Herein we describe our discovery of quinolone derivatives, novel small-molecules that inhibit NS5b polymerase, a key enzyme of the viral life-cycle. Our SAR led us from keto-quinolones such as 2 to benzyl esters such as 19 with attractive enzyme inhibition and cell-based replicon activity. This class of compounds binds to an allosteric site of NS5B polymerase (NNI-2) as confirmed through a co-crystal structure of a representative compound to NS5B.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 1, 1 January 2011, Pages 82-87
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 1, 1 January 2011, Pages 82-87
نویسندگان
Dange V. Kumar, Roopa Rai, Ken A. Brameld, John R. Somoza, Ravi Rajagopalan, James W. Janc, Yu M. Xia, Tony L. Ton, Michael B. Shaghafi, Huiyong Hu, Isabelle Lehoux, Nhat To, Wendy B. Young, Michael J. Green,