Bioorganic and Medicinal Chemistry Letters p. 4056 - 4060 (2017)
Update date:2022-08-05
Topics:
Wang, Cailan
Corte, James R.
Rossi, Karen A.
Bozarth, Jeffrey M.
Wu, Yiming
Sheriff, Steven
Myers, Joseph E.
Luettgen, Joseph M.
Seiffert, Dietmar A.
Wexler, Ruth R.
Quan, Mimi L.
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.
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