کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10595998 981883 2013 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor
چکیده انگلیسی
A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design. An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation. Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model. A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 8, 15 April 2013, Pages 2432-2435
نویسندگان
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