کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1363372 | 981510 | 2010 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Towards the second generation of Boceprevir: Dithianes as an alternative P2 substituent for 2,2-dimethyl cycloproyl proline in HCV NS3 protease inhibitors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Towards the second generation of Boceprevir: Dithianes as an alternative P2 substituent for 2,2-dimethyl cycloproyl proline in HCV NS3 protease inhibitors Towards the second generation of Boceprevir: Dithianes as an alternative P2 substituent for 2,2-dimethyl cycloproyl proline in HCV NS3 protease inhibitors](/preview/png/1363372.png)
چکیده انگلیسی
Hepatitis C (HCV) infection is a global health crisis leading to chronic liver disease. In our efforts towards a second generation HCV NS3 serine protease inhibitor with improved profile, we have undertaken SAR studies in various regions of Boceprevir including P2. Herein, we report the synthesis and structure–activity relationship studies of inhibitors with (S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid 2 as P2 substituent replacing the (1R,2S,5S)-6,6-dimethyl 3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The systematic investigation led to the discovery of highly potent inhibitor 25 (Ki∗ = 7 nM, EC90 = 30 nM) with improved rat exposure of 2.56 μM h.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 5, 1 March 2010, Pages 1689–1692
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 5, 1 March 2010, Pages 1689–1692
نویسندگان
Latha G. Nair, Stephane Bogen, Sumei Ruan, Weidong Pan, Russel Pike, Xiao Tong, Kuo-Chi Cheng, Zhuyan Guo, Ronald J. Doll, F. George Njoroge,