Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595998 | Bioorganic & Medicinal Chemistry Letters | 2013 | 4 Pages |
Abstract
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.
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Authors
E. Scott Priestley, Indawati De Lucca, Jinglan Zhou, Jiacheng Zhou, Eddine Saiah, Robert Stanton, Leslie Robinson, Joseph M. Luettgen, Anzhi Wei, Xiao Wen, Robert M. Knabb, Pancras C. Wong, Ruth R. Wexler,