1. Macrocyclic factor XIa inhibitors.
- Author
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Wang, Cailan, Corte, James R., Rossi, Karen A., Bozarth, Jeffrey M., Wu, Yiming, Sheriff, Steven, Jr.Myers, Joseph E., Luettgen, Joseph M., Seiffert, Dietmar A., Wexler, Ruth R., and Quan, Mimi L.
- Subjects
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MACROCYCLIC compounds , *CRYSTAL structure , *SERINE proteinase inhibitors , *STRUCTURAL design , *THROMBOPLASTIN - Abstract
A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the crystal structures of the acyclic phenylimidazole compounds. Further optimization using structure-based design led to inhibitors with pM affinity for FXIa, excellent selectivity against a panel of relevant serine proteases, and good potency in the activated partial thromboplastin time (aPTT) clotting assay. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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