کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1370320 | 981816 | 2013 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Design and synthesis of bicyclic pyrazinone and pyrimidinone amides as potent TF–FVIIa inhibitors
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Bicyclic pyrazinone and pyrimidinone amides were designed and synthesized as potent TF–FVIIa inhibitors. SAR demonstrated that the S2 and S3 pockets of FVIIa prefer to bind small, lipophilic groups. An X-ray crystal structure of optimized compound 9b bound in the active site of FVIIa showed that the bicyclic scaffold provides 5 hydrogen bonding interactions in addition to projecting groups for interactions within the S1, S2 and S3 pockets. Compound 9b showed excellent FVIIa potency, good selectivity against FIXa, Xa, XIa and chymotrypsin, and good clotting activity.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 6, 15 March 2013, Pages 1604–1607
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 6, 15 March 2013, Pages 1604–1607
نویسندگان
Xiaojun Zhang, Peter W. Glunz, Wen Jiang, Aaron Schmitt, Makenzie Newman, Frank A. Barbera, Jeffery M. Bozarth, Alan R. Rendina, Anzhi Wei, Xiao Wen, Karen A. Rossi, Joseph M. Luettgen, Pancras C. Wong, Robert M. Knabb, Ruth R. Wexler,